Mutant of homoserine dehydrogenase from Corynebacterium and DNA encoding thereof

ABSTRACT

Novel polynucleotides derived from microorganisms belonging to coryneform bacteria and fragments thereof, polypeptides encoded by the polynucleotides and fragments thereof, polynucleotide arrays comprising the polynucleotides and fragments thereof, recording media in which the nucleotide sequences of the polynucleotide and fragments thereof have been recorded which are readable in a computer, and use of them.

The present application is a divisional of application Ser. No.09/738,626, filed Monday, Dec. 18, 2000 now abandoned, the entirecontents of which is hereby incorporated by reference.

The present application claims benefit of Japanese Patent ApplicationNos. Hei. 11-377484 (filed Dec. 16, 1999), 2000-159162 (filed Apr. 7,2000) and 2000-280988 (filed Aug. 3, 2000), the entire contents of eachof which is incorporated herein by reference.

The contents of the attached 3 CD-R compact discs (COPY 1 REPLACEMENTJun. 12, 2006, COPY 2 REPLACEMENT Jun. 21, 2006 and COPY 3 REPLACEMENTJun. 12, 2006) are incorporated herein by reference in their entirety.The attached discs contain an identical copy of a file “249-125.txt”which were created Jun. 8, 2001, and are each 25904 KB. The SequenceListings filed in the parent application Ser. No. 09/738,626 on Dec. 18,2000 and Jun. 29, 2001, are incorporated herein by reference. TheSequence Listing contained on the attached discs are the same as the“paper” and computer readable copies of the Sequence Listing filed inthe parent application Ser. No. 09/738,626 on Dec. 18, 2000 and Jun. 29,2001.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to novel polynucleotides derived frommicroorganisms belonging to coryneform bacteria and fragments thereof,polypeptides encoded by the polynucleotides and fragments thereof,polynucleotide arrays comprising the polynucleotides and fragmentsthereof, computer readable recording media in which the nucteotidesequences of the polynucleotide and fragments thereof have beenrecorded, and use of them as well as a method of using thepolynucleotide and/or polypeptide sequence information to makecomparisons.

2. Brief Description of the Background Art

Coryneform bacteria are used in producing various useful substances,such as amino acids, nucleic acids, vitamins, saccharides (for example,ribulose), organic acids (for example, pyruvic acid), and analogues ofthe above-described substances (for example, N-acetylamino acids) andare very useful microorganisms industrially. Many mutants thereof areknown.

For example, Corynebacterium glutamicum is a Gram-positive bacteriumidentified as a glutamic acid-producing bacterium, and many amino acidsare produced by mutants thereof. For example, 1,000,000 ton/year ofL-glutamic acid which is useful as a seasoning for umami (delicioustaste), 250,000 ton/year of L-lysine which is a valuable additive forlivestock feeds and the like, and several hundred ton/year or more ofother amino acids, such as L-arginine, L-proline, L-glutamine,L-tryptophan, and the like, have been produced in the world (Nikkei BioYearbook 99, published by Nikkei BP (1998)).

The production of amino acids by Corynebacterium glutamicum is mainlycarried out by its mutants (metabolic mutants) which have a mutatedmetabolic pathway and regulatory systems. In general, an organism isprovided with various metabolic regulatory systems so as not to producemore amino acids than it needs. In the biosynthesis of L-lysine, forexample, a microorganism belonging to the genus Corynebacterium is undersuch regulation as preventing the excessive production by concertedinhibition by lysine and threonine against the activity of abiosynthesis enzyme common to lysine, threonine and methionine, i.e., anaspartokinase, (J. Biochem., 65: 849-859 (1969)). The biosynthesis ofarginine is controlled by, repressing the expression of its biosynthesisgene by arginine so as not to biosynthesize an excessive amount ofarginine (Microbiology, 142: 99-108 (1996)). It is considered that thesemetabolic regulatory mechanisms are deregulated in amino acid-producingmutants. Similarly, the metabolic regulation is deregulated in mutantsproducing nucleic acids, vitamins, saccharides, organic acids andanalogues of the above-described substances so as to improve theproductivity of the objective product.

However, accumulation of basic genetic, biochemical and molecularbiological data on coryneform bacteria is insufficient in comparisonwith Escherichia coli, Bacillus subtilis, and the like. Also, fewfindings have been obtained on mutated genes in amino acid-producingmutants. Thus, there are various mechanisms, which are still unknown, ofregulating the growth and metabolism of these microorganisms.

A chromosomal physical map of Corynebacterium glutamicum ATCC 13032 isreported and it is known that its genome size is about 3,100 kb (Mol.Gen. Genet., 252: 255-265 (1996)). Calculating on the basis of the usualgene density of bacteria, it is presumed that about 3,000 genes arepresent in this genome of about 3,100 kb. However, only about 100 genesmainly concerning amino acid biosynthesis genes are known inCorynebacterium glutamicum, and the nucleotide sequences of most geneshave not been clarified hitherto.

In recent years, the full nucleotide sequence of the genomes of severalmicroorganisms, such as Escherichia coli, Mycobacterium tuberculosis,yeast, and the like, have been determined (Science, 277: 1453-62 (1997);Nature, 393: 537-544 (1998); Nature, 387: 5-105 (1997)). Based on thethus determined full nucleotide sequences, assumption of gene regionsand prediction of their function by comparison with the nucleotidesequences of known genes have been carried out. Thus, the functions of agreat number of genes have been presumed, without genetic, biochemicalor molecular biological experiments.

In recent years, moreover, techniques for monitoring expression levelsof a great number of genes simultaneously or detecting mutations, usingDNA chips, DNA arrays or the like in which a partial nucleic acidfragment of a gene or a partial nucleic acid fragment in genomic DNAother than a gene is fixed to a solid support, have been developed. Thetechniques contribute to the analysis of microorganisms, such as yeasts,Mycobacterium tuberculosis, Mycobacterium bovis used in BCG vaccines,and the like (Science, 278: 680-686 (1997); Proc. Natl. Acad. Sci. USA,96: 12833-38 (1999); Science, 284: 1520-23 (1999)).

SUMMARY OF THE INVENTION

An object of the present invention is to provide a polynucleotide and apolypeptide derived from a microorganism of coryneform bacteria whichare industrially useful, sequence information of the polynucleotide andthe polypeptide, a method for analyzing the microorganism, an apparatusand a system for use in the analysis, and a method for breeding themicroorganism.

The present invention provides a polynucleotide and an oligonucleotidederived from a microorganism belonging to coryneform bacteria,oligonucleotide arrays to which the polynucleotides and theoligonucleotides are fixed, a polypeptide encoded by the polynucleotide,an antibody which recognizes the polypeptide, polypeptide arrays towhich the polypeptides or the antibodies are fixed, a computer readablerecording medium in which the nucleotide sequences of the polynucleotideand the oligonucleotide and the amino acid sequence of the polypeptidehave been recorded, and a system based on the computer using therecording medium as well as a method of using the polynucleotide and/orpolypeptide sequence information to make comparisons.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a map showing the positions of typical genes on the genome ofCorynebacterium glutamicum ATCC 13032.

FIG. 2 is electrophoresis showing the results of proteome analyses usingproteins derived from (A) Corynebacterium glutamicum ATCC 13032, (B)FERM BP-7134, and (C) FERM BP-158.

FIG. 3 is a flow chart of an example of a system using the computerreadable media according to the present invention.

FIG. 4 is a flow chart of an example of a system using the computerreadable media according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

This application is based on Japanese applications No. Hei. 11-377484filed on Dec. 16, 1999, No. 2000-159162 filed on Apr. 7, 2000 and No.2000-280988 filed on Aug. 3, 2000, the entire contents of which areincorporated hereinto by reference.

From the viewpoint that the determination of the full nucleotidesequence of Corynebacterium glutamicum would make it possible to specifygene regions which had not been previously identified, to determine thefunction of an unknown gene derived from the microorganism throughcomparison with nucleotide sequences of known genes and amino acidsequences of known genes, and to obtain a useful mutant based on thepresumption of the metabolic regulatory mechanism of a useful product bythe microorganism, the inventors conducted intensive studies and, as aresult, found that the complete genome sequence of Corynebacteriumglutamicum can be determined by applying the whole genome shotgunmethod.

Specifically, the present invention relates to the following (1) to(65):

-   (1) A method for at least one of the following:-   (A) identifying a mutation point of a gene derived from a mutant of    a coryneform bacterium,-   (B) measuring an expression amount of a gene derived from a    coryneform bacterium,-   (C) analyzing an expression profile of a gene derived from a    coryneform bacterium,-   (D) analyzing expression patterns of genes derived from a coryneform    bacterium, or-   (E) identifying a gene homologous to a gene derived from a    coryneform bacterium,    -   said method comprising:-   (a) producing a polynucleotide array by adhering to a solid support    at least two polynucleotides selected from the group consisting of    first polynucleotides comprising the nucleotide sequence represented    by any one of SEQ ID NOS:1 to 3501, second polynucleotides which    hybridize with the first polynucleotides under stringent conditions,    and third polynucleotides comprising a sequence of 10 to 200    continuous bases of the first or second polynucleotides,-   (b) incubating the polynucleotide array with at least one of a    labeled polynucleotide derived from a coryneform bacterium, a    labeled polynucleotide derived from a mutant of the coryneform    bacterium or a labeled polynucleotide to be examined, under    hybridization conditions,-   (c) detecting any hybridization, and-   (d) analyzing the result of the hybridization.

As used herein, for example, the at least two polynucleotides can be atleast two of the first polynucleotides, at least two of the secondpolynucleotides, at least two of the third polynucleotides, or at leasttwo of the first, second and third polynucleotides.

-   (2) The method according to (1), wherein the coryneform bacterium is    a microorganism belonging to the genus Corynebacterium, the genus    Brevibacterium, or the genus Microbacterium.-   (3) The method according to (2), wherein the microorganism belonging    to the genus Corynebacterium is selected from the group consisting    of Corynebacterium glutamicum, Corynebacterium acetoacidophilum,    Corynebacterium acetoglutamicum, Corynebacterium callunae,    Corynebacterium herculis, Corynebacterium lilium, Corynebacterium    melassecola, Corynebacterium thermoaminogenes, and Corynebacterium    ammoniagenes.-   (4) The method according to (1), wherein the polynucleotide derived    from a coryneform bacterium, the polynucelotide derived from a    mutant of the coryneform bacterium or the polynucleotide to be    examined is a gene relating to the biosynthesis of at least one    compound selected from an amino acid, a nucleic acid, a vitamin, a    saccharide, an organic acid, and analogues thereof.-   (5) The method according to (1), wherein the polynucleotide to be    examined is derived from Escherichia coli.-   (6) A polynucleotide array, comprising:    -   at least two polynucleotides selected from the group consisting        of first polynucleotides comprising the nucleotide sequence        represented by any one of SEQ ID NOS:1 to 3501, second        polynucleotides which hybridize with the first polynucleotides        under stringent conditions, and third polynucleotides comprising        10 to 200 continuous bases of the first or second        polynucleotides, and    -   a solid support adhered thereto.

As used herein, for example, the at least two polynucleotides can be atleast two of the first polynucleotides, at least two of the secondpolynucleotides, at least two of the third polynucleotides, or at leasttwo of the first, second and third polynucleotides.

-   (7) A polynucleotide comprising the nucleotide sequence represented    by SEQ ID NO:1 or a polynucleotide having a homology of at least 80%    with the polynucleotide.

(8) A polynucleotide comprising any one of the nucleotide sequencesrepresented by SEQ ID NOS:2 to 3431, or a polynucleotide whichhybridizes with the polynucleotide under stringent conditions.

-   (9) A polynucleotide encoding a polypeptide having any one of the    amino acid sequences represented by SEQ ID NOS:3502 to 6931, or a    polynucleotide which hybridizes therewith under stringent    conditions.-   (10) A polynucleotide which is present in the 5′ upstream or 3′    downstream of a polynucleotide comprising the nucleotide sequence of    any one of SEQ ID NOS:2 on 3431 in a whole polynucleotide comprising    the nucleotide sequence represented by SEQ ID NO:1, and has an    activity of regulating an expression of the polynucleotide.-   (11) A polynucleotide comprising 10 to 200 continuous bases in the    nucleotide sequence of the polynucleotide of any one of (7) to (10),    or a polynucleotide comprising a nucleotide sequence complementary    to tie polynucleotide comprising 10 to 200 continuous based.-   (12) A recombinant DNA comprising the polynucleotide of any one    of (8) to (11).-   (13) A transformant comprising the polynucleotide of any one of (8)    to (11) or the recombinant DNA of (12).-   (14) A method for producing a polypeptide, comprising:    -   culturing the transformant of (13) in a medium to produce and        accumulate a polypeptide encoded by the polynucleotide of (8)        or (9) in the medium, and    -   recovering the polypeptide from the medium.-   (15) A method for producing at least one of an amino acid, a nucleic    acid, a vitamin, a saccharide, an organic acid, and analogues    thereof, comprising:    -   culturing the transformant of (13) in a medium to produce and        accumulate at least one of an amino acid, a nucleic acid, a        vitamin, a saccharide, an organic acid, and analogues thereof in        the medium, and    -   recovering the at least one of the amino acid, the nucleic acid,        the vitamin, the saccharide, the organic acid, and analogues        thereof from the medium.-   (16) A polypeptide encoded by a polynucleotide comprising the    nucleotide sequence selected from SEQ ID NOS:2 to 3431.-   (17) A polypeptide comprising the amino acid sequence selected from    SEQ ID NOS:3502 to 6931.-   (18) The polypeptide according to (16) or (17), wherein at least one    amino acid is deleted, replaced, inserted or added, said    polypeptides having an activity which is substantially the same as    that of the polypeptide without said at least one amino acid    deletion, replacement, insertion or addition.-   (19) A polypeptide comprising an amino acid sequence having a    homology of at least 60% with the amino acid sequence of the    polypeptide of (16) or (17), and having an activity which is    substantially the same as that of the polypeptide.-   (20) An antibody which recognizes the polypeptide of any one of (16)    to (19).-   (21) A polypeptide array, comprising:    -   at least one polypeptide or partial fragment polypeptide        selected from the polypeptides of (16) to (19) and partial        fragment polypeptides of the polypeptides, and    -   a solid support adhered thereto.-   (22) A polypeptide array, comprising:    -   at least one antibody which recognizes a polypeptide or partial        fragment polypeptide selected from the polypeptides of (16)        to (19) and partial fragment polypeptides of the polypeptides,        and    -   a solid support adhered thereto.-   (23) A system based on a computer for identifying a target sequence    or a target structure motif derived from a coryneform bacterium,    comprising the following:-   (i) a user input device that inputs at least one nucleotide sequence    information selected from SEQ ID NOS:1 to 3501, and target sequence    or target structure motif information;-   (ii) a data storage device for at least temporarily storing the    input information;-   (iii) a comparator that compares the at least one nucleotide    sequence information selected from SEQ ID NOS:1 to 3501 with the    target sequence or target structure motif information, recorded by    the data storage device for screening and analyzing nucleotide    sequence information which is coincident with or analogous to the    target sequence or target structure motif information; and-   (iv) an output device that shows a screening or analyzing result    obtained by the comparator.-   (24) A method based on a computer for identifying a target sequence    or a target structure motif derived from a coryneform bacterium,    comprising the following:-   (i) inputting at least one nucleotide sequence, information selected    from SEQ ID NOS:1 to 3501, target sequence information or target    structure motif information into a user input device;-   (ii) at least temporarily storing said information;-   (iii) comparing the at least one nucleotide sequence information    selected from SEQ ID NOS:1 to 3501 with the target sequence or    target structure motif information; and-   (iv) screening and analyzing nucleotide sequence information which    is coincident with or analogous to the target sequence or target    structure motif information.-   (25) A system based on a computer for identifying a target sequence    or a target structure motif derived from a coryneform bacterium,    comprising the following:-   (i) a user input device that inputs at least one amino acid sequence    information selected from SEQ ID NOS:3502 to 7001, and target    sequence or target structure motif information;-   (ii) a data storage device for at least temporarily storing the    input information;-   (iii) a comparator that compares the at least one amine acid    sequence information selected from SEQ ID NOS:3502 to 7001 with the    target sequence or target structure motif information, recorded by    the data storage device for screening and analyzing amino acid    sequence information which is coincident with or analogous to the    target sequence or target structure motif information; and-   (iv) an output device that shows a screening or analyzing result    obtained by the comparator.-   (26) A method based on a computer for identifying a target sequence    or a target structure motif derived from a coryneform bacterium,    comprising the following:-   (i) inputting at least one amino acid sequence information selected    from SEQ ID NOS:3502 to 7001, and target sequence information or    target structure motif information into a user input device;-   (ii) at least temporarily storing said information;-   (iii) comparing the at least one amino acid sequence information    selected from SEQ ID NOS:3502 to 7001 with the target sequence or    target structure motif information; and-   (iv) screening and analyzing amino acid sequence information which    is coincident with or analogous to the target sequence or target    structure motif information.-   (27) A system based on a computer for determining a function of a    polypeptide encoded by a polynucleotide having a target nucleotide    sequence derived from a coryneform bacterium, comprising the    following:-   (i) a user input device that inputs at least one nucleotide sequence    information selected from SEQ ID NOS:2 to 3501, function information    of a polypeptide encoded by the nucleotide sequence, and target    nucleotide sequence information;-   (ii) a data storage device for at least temporarily storing the    input information;-   (iii) a comparator that compares the at least one nucleotide    sequence information selected from SEQ ID NOS:2 to 3501 with the    target nucleotide sequence information, and determining a function    of a polypeptide encoded by a polynucleotide having the target    nucleotide sequence which is coincident with or analogous to the    polynucleotide having at least one nucleotide sequence selected from    SEQ ID NOS:2 to 3501; and-   (iv) an output devices that shows a function obtained by the    comparator.-   (28) A method based on a computer for determining a function of a    polypeptide encoded by a polypeptide encoded by a polynucleotide    having a target nucleotide sequence derived from a coryneform    bacterium, comprising the following:-   (i) inputting at least one nucleotide sequence information selected    from SEQ ID NOS:2 to 3501, function information of a polypeptide    encoded by the nucleotide sequence, and target nucleotide sequence    information;-   (ii) at least temporarily storing said information;-   (iii) comparing the at least one nucleotide sequence information    selected from SEQ ID NOS:2 to 3501 with the target nucleotide    sequence information; and-   (iv) determining a function of a polypeptide encoded by a    polynucleotide having the target nucleotide sequence which is    coincident with or analogous to the polynucleotide having at least    one nucleotide sequence selected from SEQ ID NOS:2 to 3501.-   (29) A system based on a computer for determining a function of a    polypeptide having a target amino acid sequence derived from a    coryneform bacterium, comprising the following:-   (i) a user input device that inputs at least one amino acid sequence    information selected from SEQ ID NOS:3502 to 7001, function    information based on the amino acid sequence, and target amino acid    sequence information;-   (ii) a data storing device for at least temporarily storing the    input information;-   (iii) a comparator that compares the at least one amino acid    sequence information selected from SEQ ID NOS:3502 to 7001 with the    target amino acid sequence information for determining a function of    a polypeptide having the target amino acid sequence which is    coincident with or analogous to the polypeptide having at least one    amino acid sequence selected from SEQ ID NOS: 3502 to 7001; and-   (iv) an output device that shows a function obtained by the    comparator.-   (30) A method based on a computer for determining a function of a    polypeptide having a target amino acid sequence derived from a    coryneform bacterium, comprising the following:-   (i) inputting at least one amino acid sequence information selected    from SEQ ID NOS: 3502 to 7001, function information based on the    amino acid sequence, and target amino acid sequence information;-   (ii) at least temporarily storing said information;-   (iii) comparing the at least one amino acid sequence information    selected from SEQ ID NOS:3502 to 7001 with the target amino acid    sequence information; and-   (iv) determining a function of a polypeptide having the target amino    acid sequence which is coincident with or analogous to the    polypeptide having at least one amino acid sequence selected from    SEQ ID NOS:3502 to 7001.-   (31) The system according to any one of (23), (25), (27) and (29),    wherein a coryneform bacterium is a microorganism of the genus    Corynebacterium, the genus Brevibacterium, or the genus    Microbacterinum-   (32) The method according to any one of (24), (26), (28) and (30),    wherein a coryneform bacterium is a microorganism of the genus    Corynebacterium, the genus Brevibacterium, or the genus    Microbacterinum.-   (33) The system according to (31), wherein the microorganism    belonging to the genus Corynebacterium is selected from the group    consisting of Corynebacterium glutamicum, Corynebacterium    acetoacidophilum, Corynebacterium acetoglutamicum, Corynebacterium    callunae, Corynebacterium herculis, Corynebacterium lilium,    Corynebacterium melassecola, Corynebacterium thermoaminogenes, and    Corynebacterium ammoniagenes.-   (34) The method according to (32), wherein the microorganism    belonging to the genus Corynebacterium is selected from the grow    consisting of Corynebacterium glutamicum, Corynebacterium    acetoacidophilum, Corynebacterium acetoglutamicum, Corynebacterium    callunae, Corynebacterium herculis, Corynebacterium lilium,    Corynebacterium melassecola, Corynebacterium thermoaminogenes, and    Corynebacterium ammoniagenes.-   (35) A recording medium or storage device which is readable by a    computer is which at least one nucleotide sequence information or    selected from SEQ ID NOS:1 to 3501 or function information based or    the nucleotide sequence is recorded, and is usuable in the system    of (23) or (27) or the method of (24) or (28)-   (36) A recording medium or storage device which is readable by a    computer in which at least one amino acid sequence information    selected from SEQ ID NOS:3502 to 7001 or function information based    on the amino acid sequence is recorded, and is usable in the system    of (25) or (29) or the method of (26) or (30).-   (37) The recording medium or storage device according to (35) or    (36), wherein is a computer readable recording medium selected from    the group consisting of a floppy disc, a hard disc, a magnetic tape,    a random access memory (RAM), a read only memory (ROM), a    magneto-optic disc (MO), CD-ROM, CD-R, CD-RW, DVD-ROM, DVD-RAM and    DVD-RW.-   (38) A polypepide having a homoserine dehydrogenase activity,    comprising an amino acid sequence in which the Val residue at the    sequence in the amino acid sequence of homoserine dehydrogenase    derived from a coryneform bacterium is replaced with amino acid    residue other than a Val residue.-   (39) A polypeptide comprising an amino acid sequence in which the    Val residue at the 59th position at the amino acid sequence as    represented by SEQ ID NO:6952 is replaced with amino acid residue    other than a Val residue.-   (40) The polypeptide according to (38) or (39) wherein the Val    residue at the 59th position is replaced with an Ala residue.-   (41) A polypeptide having private carboxylase activity, comprising    an amino acid sequence in which the Pro residue at the 458th    position in the amino acid sequence of private carboxylase derived    from a coryneform bacterium is replaced with an amino acid residue    other than a Pro residue.-   (42) A polypeptide cruising an amino acid sequence in which the Pro    residue at the 458th position in the amino acid sequence represented    by SEQ ID NO:4265 is replaced with an amino acid residue other than    a Pro residue.-   (43) The polypeptide according to (41) or (42), wherein the Pro    residue at the 458th position is replaced with a Ser residue.-   (44) The polypeptide recording to any one of (38) to (43), which is    derived from Corynebacterium glutamicum.-   (45) A DNA encoding the polypeptide of any one of (38) to (44).-   (46) A recombinant DNA comprising the DNA of (45).-   (47) A transformant comprising the recombinant DNA of (46).-   (48) A transformant comprising in its chromosome the DNA of (45).-   (49) The transformant according to (47) or (48), which is derived    from a coryneform bacterium.-   (50) The transformant according to (49), which is derived from    Corynebacterium glutamicum.-   (51) A method for producing L-lysine, comprising:-   culturing the transformant of any one of (47) to (50) in a medium to    produce and accumulate L-lysine in the medium, and recovering the    L-lysine from the culture.-   (52) A method for breeding a coryneform bacterium using the    nucleotide sequence information represented by SEQ ID NOS:1 to 3431,    comprising the following:-   (i) comparing a nucleotide sequence of a genome or gene of a    production strain derived a coryneform bacterium which has been    subjected to mutation breeding 50 as the produce at least one    compound selected from an amino acid, a nucleic acid, a vitamin, a    saccharide, an organic acid, and analogous thereof by a fermentation    method with a corresponding nucleotide sequence in SEQ ID NOS:1 to    3431;-   (ii) identifying a mutation point present in the production strain    based on a result obtained by the-   (iii) introducing the mutation point into a coryneform bacterium    which is free of the mutation point; and-   (iv) examining productivity by the fermentation method of the    compound selected in (i) of the coryneform bacterium obtained in    (iii)-   (53) The method according to (52), wherein the gene is a gene    encoding an enzyme in a biosynthesis pathway or a signal    transmission pathway.-   (54) The method according to (52), wherein the mutation point is a    mutation point relating to a useful mutation which improves or    stabilizes the productivity.-   (55) A method for breading a coryneform bacterium using the    nucleotide sequence information represented by SEQ ID NOS:1 to 3431,    comprising:-   (i) comparing a nucleotide sequence of a genome or gene of a    production strain derived a coryneform bacterium which has been    subjected to mutation breeding so as to produce at least one    compound selected from an amino acid, a nucleic acid, a vitamin a    saccharide, an organic acid, and analogous thereof by a fermentation    method, with a corresponding nucleon of sequence in SEQ ID NOS:1 to    3431;-   (ii) identifying a mutation point present in the production strain    based on the result obtain by (i);-   (iii) deleting a mutation point from a coryneform bacterium having    the mutation point; and-   (iv) examining productivity by the fermentation method of the    compound selected in (i) of the coryneform bacterium obtained in    (iii).-   (56) The method according to (55), wherein the gene is a gene    encoding an enzyme in a biosynthesis pathway or a signal    transmission pathway.-   (57) The method according to (55), wherein the mutation point is a    mutation point which decreases or destabilizes the productivity.-   (58) A method for breeding a coryneform bacterium using the    nucleotide sequence information represented by SEQ ID NOS:2 to 3431,    comprising the following:-   (i) identifying an isozyme relating to biosynthesis of at least one    compound selected from an amino acid, a nucleic acid, a vitamin, a    saccharide, an organic acid, and analogous thereof, based on the    nucleotide sequence information represented by SEQ ID NOS:2 to 3431;-   (ii) classifying the isozyme identified in (i) into an isozyme    having the same activity;-   (iii) mutating all genes encoding the isozyme having the same    activity simultaneously; and-   (iv) examining productivity by a fermentation method of the compound    selected in (i) of the coryneform bacterium which have been    transforms with the gene obtained in (iii)-   (59) A method for breeding a coryneform bacterium using the    nucleotide sequence information represented by SEQ ID NOS:2 to 3431,    comprising the following:-   (i) arranging a function information of an open reading frame (ORF)    represented by SEQ ID NOS:2 to 3431;-   (ii) allowing the arranged ORF to correspond to an enzyme on a known    biosynthesis or signal transmission pathway;-   (iii) explicating an unknown biosynthesis pathway or signal    transmission pathway of a coryneform bacterium in combination with    information relating known biosynthesis pathway or signal    transmission pathway of a coryneform bacterium;-   (iv) comparing the pathway explicated in (iii) with a biosynthesis    pathway of a target useful product; and-   (v) transgenetically varying a coryneform bacterium based on the    nucleotide sequence information to either strengthen a pathway which    is judged to be important in the biosynthesis of the target useful    product in (iv) or weaken a pathway which is judged not to be    important in the biosynthesis of the target useful product in (iv).-   (60) A coryneform bacterium, bread by the method of any one of (52)    to (59).-   (61) The coryneform bacterium according to (60), which is a    microorganism belonging to the genus Corynebacterium, the genus    Brevibacterium, or the genus Microbacterium.-   (62) The coryneform bacterium according to (61), wherein the    microorganism belonging to the genus Corynebacterium is selected    from the group consisting of Corynebacterium glutamicum,    Corynebacterium acetoacidophilum, Corynebacterium acetoglutamicum,    Corynebacterium callunae, Corynebacterium herculis, Corynebacterium    lilium, Corynebacterium melassecola, Corynebacterium    thermoaminogenes, and Corynebacterium ammoniagenes.-   (63) A method for producing at least one compound selected from an    amino acid, a nucleic acid, a vitamin, a saccharide, an organic acid    and an analogue thereof, comprising:    -   culturing a coryneform bacterium of any one of (60) to (62) in a        medium to produce and accumulate at least one compound selected        from an amino acid, a nucleic acid, a vitamin, a saccharide, an        organic acid, and analogues thereof;    -   recovering the compound from the culture.-   (64) The method according to (63), wherein the compound is L-lysine.-   (65) A method for identifying a protein relating to useful mutation    based on proteome analysis, comprising the following:-   (i) preparing    -   a protein derived from a bacterium of a production strain of a        coryneform bacterium which has been subjected to mutation        breeding by a fermentation process so as to produce at least one        compound selected from an amino acid, a nucleic acid, a vitamin,        a saccharide, an organic acid, and analogues thereof, and    -   a protein derived from a bacterium of a parent strain of the        production strain;-   (ii) separating the proteins prepared in (i) by two dimensional    electrophoresis;-   (iii) detecting the separated proteins, and comparing an expression    amount of the protein derived from the production strain with that    derived from the parent strain;-   (iv) treating the protein showing different expression amounts as a    result of the comparison with a peptidase to extract peptide    fragments;-   (v) analyzing amino acid sequences of the peptide fragments obtained    in (iv); and-   (vi) comparing the amino acid sequences obtained in (v) with the    amino acid sequence represented by SEQ ID NOS:3502 to 7001 to    identifying the protein having the amino acid sequences.

As used herein, the term “proteome”, which is a coined word by combining“protein” with “genome”, refers to a method for examining of a gene atthe polypeptide level.

-   (66) The method according to (65), wherein the coryneform bacterium    is a microorganism belonging to the genus Corynebacterium, the genus    Brevibacterium, or the genus Microbacterium.-   (67) The method according to (66), wherein the microorganism    belonging to the genus Corynebacterium is selected from the group    consisting of Corynebacterium glutamicum, Corynebacterium    acetoacidophilum, Corynebacterium acetoglutamicum, Corynebacterium    callunae, Corynebacterium herculis, Corynebacterium lilium,    Corynebacterium melassecola, Corynebacterium thermoaminogenes, and    Corynebacterium ammoniagenes.-   (68) A biologically pure culture of Corynebacterium glutamicum AHP-3    (FERN BP-7382).

The present invention will be described below in more detail, based onthe determination of the full nucleotide sequence of coryneformbacteria.

1. Determination of Full Nucleotide Sequence of Coryneform Bacteria

The term “coryneform bacteria” as used herein means a microorganismbelonging to the genus Corynebacterium, the genus Brevibacterium or thegenus Microbacterium as defined in Bergeys Manual of DeterminativeBacteriology, 8: 599 (1974).

Examples include Corynebacterium acetoacidophilum, Corynebacteriumacetoglutamicum, Corynebacterium callunae, Corynebacterium glutamicum,Corynebacterium herculis, Corynebacterium lilium, Corynebacteriummelassecola, Corynebacterium thermoaminogenes, Brevibacteriumsaccharolyticum, Brevibacterium immariophilum, Brevibacterium roseum,Brevibacterium thiogenitalis, Microbacterium ammoniaphilum, and thelike.

Specific examples include Corynebacterium acetoacidophilum ATCC 13870,Corynebacterium acetoglutamicum ATCC 15806, Corynebacterium callunaeATCC 15991, Corynebacterium glutamicum ATCC 13032, Corynebacteriumglutamicum ATCC 13060, Corynebacterium glutamicum ATCC 13826 (priorgenus and species: Brevibacterium flavum, or Corynebacteriumlactofermentum) Corynebacterium glutamicum ATCC 14020 (prior genus andspecies: Brevibacterium divaricatum), Corynebacterium glutamicum ATCC13869 (prior genus and species: Brevibacterium lactofermentum),Corynebacterium herculis ATCC 13868, Corynebacterium lilium ATCC 15990,Corynebacterium melassecola ATCC 17965, Corynebacterium thermoaminogenesFERM 9244, Brevibacterium saccharolyticum ATCC 4066, Brevibacteriumimmariophilum ATCC 14068, Brevibacterium roseum ATCC 13825,Brevibacterium thiogenitalis ATCC 19240, Microbacterium ammoniaphilumATCC 15354, and the like.

(1) Preparation of Genome DNA of Coryneform Bacteria

Coryneform bacteria can be cultured by a conventional method.

Any of a natural medium and a synthetic medium can be used, so long asit is a medium suitable for efficient culturing of the microorganism,and it contains a carbon source, a nitrogen source, an inorganic salt,and the like which can be assimilated by the microorganism.

In Corynebacterium glutamicum, for example, a BY medium (7 g/l meatextract, 10 g/l peptone, 3 g/l sodium chloride, 5 g/l yeast extract, pH7.2) containing 1% of glycine and the like can be used. The culturing iscarried out at 25 to 35° C. overnight.

After the completion of the culture, the cells are recovered from theculture by centrifugation. The resulting cells are washed with a washingsolution.

Examples of the washing solution include STE buffer (10.3% sucrose, 25mmol/l Tris hydrochloride, 25 mmol/l ethylenediaminetetraacetic acid(hereinafter referred to as “EDTA”), pH 8.0), and the like.

Genome DNA can be obtained from the washed cells according to aconventional method for obtaining genome DNA, namely, lysing the cellwall of the cells using a lysozyme and a surfactant (SDS, etc.),eliminating proteins and the like using a phenol solution and aphenol/chloroform solution, and then precipitating the genome DNA withethanol or the like. Specifically, the following method can beillustrated.

The washed cells are suspended in a washing solution containing 5 to 20mg/l lysozyme. After shaking, 5 to 20% SDS is added to lyse the cells.In usual, shaking is gently performed at 25 to 40° C. for 30 minutes to2 hours. After shaking, the suspension is maintained at 60 to 70° C. for5 to 15 minutes for the lysis.

After the lysis, the suspension is cooled to ordinary temperature, and 5to 20 ml of Tris-neutralized phenol is added thereto, followed by gentlyshaking at room temperature for 15 to 45 minutes.

After shaking, centrifugation (15,000×g, 20 minutes, 20° C.) is carriedout to fractionate the aqueous layer.

After performing extraction with phenol/chloroform and extraction withchloroform (twice) in the same manner, 3 mol/l sodium acetate solution(pH 5.2) and isopropanol are added to the aqueous layer at 1/10 timesvolume and 2 times volume, of the aqueous layer, respectively, followedby gently stirring to precipitate the genome DNA.

The genome DNA is dissolved again in a buffer containing 0.01 to 0.04mg/ml RNase. As an example of the buffer, TE buffer (10 mmol/l Trishydrochloride, 1 mol/l EDTA, pH 8.0) can be used. After dissolving, theresultant solution is maintained at 25 to 40° C. for 20 to 50 minutesand then extracted successively with phenol, phenol/chloroform andchloroform as in the above case.

After the extraction, isopropanol precipitation is carried out and theresulting DNA precipitate is washed with 70% ethanol, followed by airdrying, and then dissolved in TE buffer to obtain a genome DNA solution.

(2) Production of Shotgun Library

A method for produce a genome DNA library using the genome DNA of thecoryneform bacteria prepared in the above (1) include a method describedin Molecular Cloning, A laboratory Manual, Second Edition (1989)(hereinafter referred to as “Molecular Cloning, 2nd ed.”). Inparticular, the following method can be exemplified to prepare a genomeDNA library appropriately usable in determining the full nucleotidesequence by the shotgun method.

To 0.01 mg of the genome DNA of the coryneform bacteria prepared in theabove (1) a buffer, such as TE buffer or the like, is added to give atotal volume of 0.4 ml. Then, the genome DNA is digested into fragmentsof 1 to 10 kb with a sonicator (Yamato Powersonic Model 50). Thetreatment with the sonicator is performed at an output off 20continuously for 5 seconds.

The resulting genome DNA fragments are blunt-ended using DNA bluntingkit (manufactured by Takara Shuzo) or the like.

The blunt-ended genome fragments are fractionated by agarose gel orpolyacrylamide gel electrophoresis and genome fragments of 1 to 2 kb areCut out from the gel.

To the gel, 0.2 to 0.5 ml of a buffer for eluting DNA, such as MGelution buffer (0.5 mol/l ammonium acetate, 10 mmol/l magnesium acetate,1 mmol/l EDTA, 0.1% SDS) or the like, is added, followed by shaking at25 to 40° C. overnight to elute DNA.

The resulting DNA eluate is treated with phenol/chloroform and thenprecipitated with ethanol to obtain a genome library insert.

This insert is ligated into a suitable vector, such as pUC18 SmaI/BAP(manufactured by Amersham Pharmacia Biotech) or the like, using T4ligase (manufactured by Takara Shuzo) or the like. The ligation can becarried out by allowing a mixture to stand at 10 to 20° C. for 20 to 50hours.

The resulting ligation product is precipitated with ethanol anddissolved in 5 to 20 μl of TE buffer.

Escherichia coli is transformed in accordance with a conventional methodusing 0.5 to 2 μl of the ligation solution. Examples of thetransformation method include the electroporation method using ELECTROMAX DH10B (manufactured by Life Technologies) for Escherichia coli. Theelectroporation method can be carved out under the conditions asdescribed in the manufacturer's instructions.

The transformed Escherichia coli is spread on a suitable selectionmedium containing agar, for example, LB plate medium containing 10 to100 mg/l ampicillin (LB medium (10 g/l bactotrypton, 5 g/l yeastextract, 10 g/l sodium chloride, pH 7.0) containing 1.6% of agar) whenpUC18 is used as the cloning vector, and cultured therein.

The transformant can be obtained as colonies formed on the plate medium.In this step, it is possible to select the transformant having therecombinant DNA containing the genome DNA as white colonies by addingX-gal and IPTG (isopropyl-β-thiogalactopyranoside) to the plate medium.

The transformant is allowed to stand for culturing in a 96-well titerplate to which 0.05 ml of the LB medium containing 0.1 mg/ml ofampicillin has been added in each well. The resulting culture can beused in an experiment of (4) described below. Also, the culture solutioncan be stored at −80° C. by adding 0.05 ml per well of the LB mediumcontaining 20% glycerol to the culture solution, followed by mixing, andthe stored culture solution can be used at any time.

(3) Production of Cosmid Library

The genome DNA (0.1 mg) of the coryneform bacteria prepared in the above(1) is partially digested with a restriction enzyme, such as Sau3AI orthe like, and then ultracentrifuged (26,000 rpm, 18 hours, 20° C.) undera 10 to 40% sucrose density gradient using a 10% sucrose buffer (1 mol/lNaCl, 20 mmol/l Tris hydrochloride, 5 mmol/l EDTA, 10% sucrose, pH 8.0)and a 40% sucrose buffer (elevating the concentration of the 10% sucrosebuffer to 40%).

After the centrifugation, the thus separated solution is fractionatedinto tubes in 1 ml per each tube. After confirming the DNA fragment sizeof each fraction by agarose gel electrophoresis, a fraction rich in DNAfragments of about 40 kb is precipitated with ethanol.

The resulting DNA fragment is ligated to a cosmid vector having acohesive end which can be ligated to the fragment. When the genome DNAis partially digested with Sau3AI, the partially digested product can beligated to, for example, the BamHI site of superCos1 (manufactured byStratagene) in accordance with the manufacture's instructions.

The resulting ligation product is packaged using a packaging extractwhich can be prepared by a method described in Molecular Cloning, 2nded. and then used in transforming Escherichia coli. More specifically,the ligation product is packaged using, for example, a commerciallyavailable packaging extract, Gigapack III Gold Packaging Extract(manufactured by Stratagene) in accordance with the manufacture'sinstructions and then introduced into Escherichia coli XL-1-BlueMR(manufactured by Stratagene) or the like.

The thus transformed Escherichia coli is spread on an LB plate mediumcontaining ampicillin, and cultured therein.

The transformant can be obtained as colonies formed on the plate medium.

The transformant is subjected to standing culture in a 96-well titerplate to which 0.05 ml of the LB medium containing 0.1 mg/ml ampicillinhas been added.

The resulting culture can be employed in an experiment of (4) describedbelow. Also, the culture solution can be stored at −80° C. by adding0.05 ml per well of the LB medium containing 20% glycerol to the culturesolution, followed by mixing, and the stored culture solution can beused at any time.

(4) Determination of Nucleotide Sequence

(4-1) Preparation of Template

The full nucleotide sequence of genome DNA of coryneform bacteria can bedetermined basically according to the whole genome shotgun method(Science, 269: 496-512 (1995) ).

The template used in the whole genome shotgun method can be prepared byPCR using the library prepared in the above (2) (DNA Research, 5: 1-9(1998)).

Specifically, the template can be prepared as follows.

The clone derived from the whole genome shotgun library is inoculated byusing a replicator (manufactured by GENETIX) into each well of a 96-wellplate to which 0.08 ml per well of the LB medium containing 0.1 mg/mlampicillin has been added, followed by stationarily culturing at 37° C.overnight.

Next, the culture solution is transported, using a copy plate(manufactured by Tokken), into each well of a 96-well reaction plate(manufactured by PE Biosystems) to which 0.025 ml per well of a PCRreaction solution has been added using TaKaRa Ex Taq (manufactured byTakara Shuzo). Then, PCR is carried out in accordance with the protocolby Makino et al. (DNA Research, 5: 1-9 (1998)) using GeneAmp PCR System9700 (manufactured by PE Biosystems) to amplify the inserted fragments.

The excessive primers and nucleotides are eliminated using a kit forpurifying a PCR product, and the product is used as the template in thesequencing reaction.

It is also possible to determine the nucleotide sequence using adouble-stranded DNA plasmid as a template.

The double-stranded DNA plasmid used as the template can be obtained bythe following method.

The clone derived from the whole genome shotgun library is inoculatedinto each well of a 24- or 96-well plate to which 1.5 ml per well of a2×YT medium (16 g/l bactotrypton, 10 g/l yeast extract, 5 g/l sodiumchloride, pH 7.0) containing 0.05 mg/ml ampicillin has been added,followed by culturing under shaking at 37° C. overnight.

The double-stranded DNA plasmid can be prepared from the culturesolution using an automatic plasmid preparing machine KURABO PI-50(manufactured by Kurabo Industries), a multiscreen (manufactured byMillipore) or the like, according to each protocol.

To purify the plasmid, Biomek 2000 manufactured by Beckman Coulter andthe like can be used.

The resulting purified double-stranded DNA plasmid is dissolved in waterto give a concentration of about 0.1 mg/ml. Then, it can be used as thetemplate in sequencing.

(4-2) Sequencing Reaction

The sequencing reaction can be carried out according to a commerciallyavailable sequence kit or the like. A specific method is exemplifiedbelow.

To 6 μl of a solution of ABI PRISM BigDye Terminator Cycle Sequencing,Ready Reaction Kit (manufactured by PE Biosystems), 1 to 2 pmol of anM13 regular direction primer (M13-21) or an M13 reverse direction primer(M13REV) (DNA Research, 5: 1-9 (1998)) and 50 to 200 ng of the templateprepared in the above (4-1) (the PCR product or plasmid) to give 10 μlof a sequencing reaction solution.

A dye terminator sequencing reaction (35 to 55 cycles) is carried outusing this reaction solution and Gene PCR System 9700 (manufactured byPE Biosystems) or the like. The cycle parameter can be determined inaccordance with a commercially available kit, for example, themanufacture's instructions attached with ABI PRISM Big Dye TerminatorCycle Sequencing Ready Reaction Kit.

The sample can be purified using a commercially available product, suchas Multi Screen HV plate (manufactured by Millipore) or the like,according to the manufacture's instructions.

The thus purified reaction product is precipitated with ethanol, driedand then used for the analysis. The dried reaction product can be storedin the dark at −30° C. and the stored reaction product can be used atany time.

The dried reaction product can be analyzed using a commerciallyavailable sequencer and an analyze according to the manufacture'sinstructions.

Examples of the commercially available sequencer include ABI PRISM 377DNA Sequencer (manufactured by PE Biosystems) Example of the analyzerinclude ABI PRISM 3700 DNA Analyzer (manufactured by PE Biosystems).

(5) Assembly

A software, such as phred (The University of Washington) or the like,can be used as base call for use in analyzing the sequence informationobtained in the above (4). A software, such as Cross_Match (TheUniversity of Washington) or SPS Cross_Match (manufactured by SouthwestParallel Software) or the like, can be used to mass the vector sequenceinformation.

For the assembly, a software, such as phrap (The University ofWashington), SPS phrap (manufactured by Southwest Parallel Software) orthe like, can be used.

In the above, analysis and output of the results thereof, a computersuch as UNIX, PC, Macintosh, and the like can be used.

Contig obtained by the assembly can be analyzed using a graphical editorsuch as consed (The University of Washington) or the like.

It is also possible to perform a series of the operations from the basecall to the assembly in a lump using a script phredPhrap attached to theconsed.

As used herein, software will be understood to also be referred to as acomparator.

(6) Determination of Nucleotide Sequence in Gap Part

Each of the cosmids in the cosmid library constructed in the above (3)is prepared in the same manner as in the preparation of thedouble-stranded DNA plasmid described in the above (4-1). The nucleotidesequence at the end of the insert fragment of the cosmid is determinedusing a commercially available kit, such as ABI PRISM BigDye TerminatorCycle Sequencing Ready Reaction Kit (manufactured by PE Biosystems)according to the manufacture's instructions.

About 800 cosmid clones are sequenced at both ends of the insertedfragment to detect a nucleotide sequence in the contig derived from theshotgun sequencing obtained in (5) which is coincident with thesequence. Thus, the chain linkage between respective cosmid clones andrespective contigs are clarified, and mutual alignment is carried out.Furthermore, the results are compared with known physical maps to mapthe cosmids and the contigs. In case of Corynebacterium glutamicum ATCC13032, a physical map of Mol. Gen. Genet., 252: 255-265 (1996) can beused.

The sequence in the region which cannot be covered with the contigs (gappart) can be determined by the following method.

Clones containing sequences positioned at the ends of the contigs areselected. Among these, a clone wherein only one end of the insertedfragment has been determined is selected and the sequence at theopposite end of the inserted fragment is determined.

A shotgun library clone or a cosmid clone derived therefrom containingthe sequences at the respective ends of the inserted fragments in thetwo contigs is identified and the full nucleotide sequence of theinserted fragment of the clone is determined.

According to this method, the nucleotide sequence of the gap part can bedetermined.

When no shotgun library clone or cosmid clone covering the gap part isavailable, primers complementary to the end sequences of the twodifferent contigs are prepared and the DNA fragment in the gap part isamplified. Then, sequencing is performed by the primer walking methodusing the amplified DNA fragment as a template or by the shotgun methodin which the sequence of a shotgun clone prepared from the amplified DNAfragment is determined. Thus, the nucleotide sequence of theabove-described region can be determined.

In a region showing a low sequence accuracy, primers are synthesizedusing AUTOFINISH function and NAVIGATING function of consed (TheUniversity of Washington), and the sequence is determined by the primerwalking method to improve the sequence accuracy.

Examples of the thus determined nucleotide sequence of the full genomeinclude the full nucleotide sequence of genome of Corynebacteriumglutamicum ATCC 13032 represented by SEQ ID NO:1.

(7) Determination of Nucleotide Sequence of Microorganism Genome DNAUsing the Nucleotide Sequence Represented by SEQ ID NO:1

A nucleotide sequence of a polynucleotide having a homology of 80% ormore with. the full nucleotide sequence of Corynebacterium glutamicumATCC 13032 represented by SEQ ID NO:1 as determined above can also bedetermined using the nucleotide sequence represented by SEQ ID NO:1, andthe polynucleotide having a nucleotide sequence having a homology of 80%or more with the nucleotide sequence represented by SEQ ID NO:1 of thepresent invention is within the scope of the present invention. The term“polynucleotide having a nucleotide sequence having a homology of 80% ormore with the nucleotide sequence represented by SEQ ID NO:1 of thepresent invention” is a polynucleotide in which a full nucleotidesequence of the chromosome DNA can be determined using as a primer anoligonucleotide composed of continuous 5 to 50 nucleotides in thenucleotide sequence represented by SEQ ID NO:1, for example, accordingto PCR using the chromosome DNA as a template. A particularly preferredprimer in determination of the full nucleotide sequence is anoligonucleotide having nucleotide sequences which are positioned at theinterval of about 300 to 500 bp, and among such oligonucleotides, anoligonucleotide having a nucleotide sequence selected from DNAs encodinga protein relating to a main metabolic pathway is particularlypreferred. The polynucleotide in which the full nucleotide sequence ofthe chromosome DNA can be determined using the oligonucleotide includespolynucleotides constituting a chromosome DNA derived from amicroorganism belonging to coryneform bacteria. Such a polynucleotide ispreferably a polynucleotide constituting chromosome DNA derived from amicroorganism belonging to the genus Corynebacterium, more preferably apolynucleotide constituting a chromosome DNA of Corynebacteriumglutamicum.

2. Identification of ORF (Open Reading Frame) and Expression RegulatoryFragment and Determination of the Function of ORF

Based on the full nucleotide sequence data of the genome derived fromcoryneform bacteria determined in the above item 1, an ORF and anexpression modulating fragment can be identified. Furthermore, thefunction of the thus determined ORF can be determined.

The ORF means a continuous region in the nucleotide sequence of mRNAwhich can be translated as an amino acid sequence to mature to aprotein. A region of the DNA coding for the ORF of mRNA is also calledORF.

The expression modulating fragment (hereinafter referred to as “EMF”) isused herein to define a series of polynucleotide fragments whichmodulate the expression of the ORF or another sequence ligatedoperatably thereto. The expression “modulate the expression of asequence ligated operatably” is used herein to refer to changes in theexpression of a sequence due to the presence of the EMF. Examples of theEMF include a promoter, an operator, an enhancer, a silencer, aribosome-binding sequence, a transcriptional termination sequence, andthe like. In coryneform bacteria, an EMF is usually present in anintergenic segment (a fragment positioned between two genes; about 10 to200 nucleotides in length). Accordingly, an EMF is frequently present inan intergenic segment of 10 nucleotides or longer. It is also possibleto determine or discover the presence of an EMF by using known EMFsequences as a target sequence or a target structural motif (or a targetmotif) using an appropriate software or comparator, such as FASTA (Proc.Natl. Acad. Sci. USA, 85: 2444-48 (1988)), BLAST (J. Mol. Biol., 215:403-410 (1990)) or the like. Also, it can be identified and evaluatedusing a known EMF-capturing vector (for example, pKK232-8; manufacturedby Amersham Pharmacia Biotech).

The term “target sequence” is used herein to refer to a nucleotidesequence composed of 6 or more nucleotides, an amino acid sequencecomposed of 2 or more amino acids, or a nucleotide sequence encodingthis amino acid sequence composed of 2 or more amino acids. A longertarget sequence appears at random in a data base at the lowerpossibility. The target sequence is preferably about 10 to 100 aminoacid residues or about 30 to 300 nucleotide residues.

The term “target structural motif” or “target motif” is used herein torefer to a sequence or a combination of sequences selected optionallyand reasonably. Such a motif is selected on the basis of thethree-dimensional structure formed by the folding of a polypeptide bymeans known to one of ordinary skill in the art. Various motives areknown.

Examples of the target motif of a polypeptide include, but are notlimited to, an enzyme activity site, a protein-protein interaction site,a signal sequence, and the like. Examples of the target motif of anucleic acid include a promoter sequence, a transcriptional regulatoryfactor binding sequence, a hair pin structure, and the like.

Examples of highly useful EMF include a high-expression promoter, aninducible-expression promoter, and the like. Such an EMF can be obtainedby positionally determining the nucleotide sequence of a gene which isknown or expected as achieving high expression (for example, ribosomalRNA gene: GenBank Accession No. M16175 or Z46753) or a gene showing adesired induction pattern (for example, isocitrate lyase gene induced byacetic acid: Japanese Published Unexamined Patent Application No.56782/93) via the alignment with the full genome nucleotide sequencedetermined in the above item 1, and isolating the genome fragment in theupstream part (usually 200 to 500 nucleotides from the translationinitiation site). It is also possible to obtain a highly useful EMF byselecting an EMF showing a high expression efficiency or a desiredinduction pattern from among promoters captured by the EMF-capturingvector as described above.

The ORF can be identified by extracting characteristics common toindividual ORFs, constructing a general model based on thesecharacteristics, and measuring the conformity of the subject sequencewith the model. In the identification, a software, such as GeneMark(Nuc. Acids. Res., 22: 4756-67 (1994): manufactured by GenePro)),GeneMark.hmm (manufactured by GenePro), GeneHacker (Protein, NucleicAcid and Enzyme, 42: 3001-07 (1997)), Glimmer (Nuc. Acids. Res., 26:544-548 (1998): manufactured by The Institute of Genomic Research), orthe like, can be used. In using the software, the default (initialsetting) parameters are usually used, though the parameters can beoptionally changed.

In the above-described comparisons, a computer, such as UNIX, PC,Macintosh, or the like, can be used.

Examples of the ORF determined by the method of the present inventioninclude ORFs having the nucleotide sequences represented by SEQ ID NOS:2to 3501 present in the genome of Corynebacterium glutamicum asrepresented by SEQ ID NO:1. In these ORFs, polypeptides having the aminoacid sequences represented by SEQ ID NOS:3502 to 7001 are encoded.

The function of an ORF can be determined by comparing the identifiedamino acid sequence of the ORF with known homologous sequences using ahomology searching software or comparator, such as BLAST, FAST, Smith &Waterman (Meth. Enzym., 164: 765 (1988)) or the like on an amino aciddata base, such as Swith-Prot, PIR, GenBank-nr-aa, GenPept constitutedby protein-encoding domains derived from GenBank data base, OWL or thelike.

Furthermore, by the homology searching, the identity and similarity withthe amino acid sequences of known proteins can also be analyzed.

With respect of the term “identity” used herein, where two polypeptideseach having 10 amino acids are different in the positions of 3 aminoacids, these polypeptides have an identity of 70% with each other. Incase wherein one of the different 3 amino acids is analogue (forexample, leucine and isoleucine), these polypeptides have a similarityof 80%.

As a specific example, Table 1 shows the registration numbers in knowndata bases of sequences which are judged as having the highestsimilarity with the nucleotide sequence of the ORF derived fromCorynebacterium glutamicum ATCC 13032, genes of these sequences,functions of these genes, and identities thereof compared with knownamino acid translation sequences.

Thus, a great number of novel genes derived from coryneform bacteria canbe identified by determining the full nucleotide sequence of the genomederived from coryneform bacterium by the means of the present invention.Moreover, the function of the proteins encoded by these genes can bedetermined. Since coryneform bacteria are industrially highly usefulmicroorganisms, many of the identified genes are industrially useful.

Moreover, the characteristics of respective microorganisms can beclarified by classifying the functions thus determined. As a result,valuable information in breeding is obtained.

Furthermore, from the ORF information derived from coryneform bacteria,the ORF corresponding to the microorganism is prepared and obtainedaccording to the general method as disclosed in Molecular Cloning, 2nded. or the like. Specifically, an oligonucleotide having a nucleotidesequence adjacent to the ORF is synthesized, and the ORF can be isolatedand obtained using the oligonucleotide as a primer and a chromosome DNAderived from coryneform bacteria as a template according to the generalPCR cloning technique. Thus obtained ORF sequences includepolynucleotides comprising the nucleotide sequence represented by anyone of SEQ ID NOS:2 to 3501.

The ORF or primer can be prepared using a polypeptide synthesizer basedon the above sequence information.

Examples of the polynucleotide of the present invention include apolynucleotide containing the nucleotide sequence of the ORF obtained inthe above, and a polynucleotide which hybridizes with the polynucleotideunder stringent conditions.

The polynucleotide of the present invention can be a single-strandedDNA, a double-stranded DNA and a single-stranded RNA, though it is notlimited thereto.

The polynucleotide which hybridizes with the polynucleotide containingthe nucleotide sequence of the ORF obtained in the above under stringentconditions includes a degenerated mutant of the ORF. A degeneratedmutant is a polynucleotide fragment having a nucleotide sequence whichis different from the sequence of the ORF of the present invention whichencodes the same amino acid sequence by degeneracy of a gene code.

Specific examples include a polynucleotide comprising the nucleotidesequence represented by any one of SEQ ID NOS:2 to 3431, and apolynucleotide which hybridizes with the polynucleotide under stringentconditions.

A polynucleotide which hybridizes under stringent conditions is apolynucleotide obtained by colony hybridization, plaque hybridization,Southern blot hybridization or the like using, as a probe, thepolynucleotide having the nucleotide sequence of the ORF identified inthe above. Specific examples include a polynucleotide which can beidentified by carrying out hybridization at 65° C. in the presence of0.7-1.0 M NaCl using a filter on which a polynucleotide prepared fromcolonies or plaques is immobilized, and then washing the filter with0.1× to 2×SSC solution (the composition of 1×SSC contains 150 mM sodiumchloride and 15 mM sodium citrate) at 65° C.

The hybridization can be carried out in accordance with known methodsdescribed in, for example, Molecular Cloning, 2nd ed., Current Protocolsin Molecular Biology, DNA Cloning 1: Core Techniques, A PracticalApproach, Second Edition, Oxford University (1995) or the like. Specificexamples of the polynucleotide which can be hybridized include a DNAhaving a homology of 60% or more, preferably 80% or more, andparticularly preferably 95% or more, with the nucleotide sequencerepresented by any one of SEQ ID NO:2 to 3431 when calculated usingdefault (initial setting) parameters of a homology searching software,such as BLAST, FASTA, Smith-Waterman or the like.

Also, the polynucleotide of the present invention includes apolynucleotide encoding a polypeptide comprising the amino acid sequencerepresented by any one of SEQ ID NOS:3502 to 6931 and a polynucleotidewhich hybridizes with the polynucleotide under stringent conditions.

Furthermore, the polynucleotide of the present invention includes apolynucleotide which is present in the 5′ upstream or 3′ downstreamregion of a polynucleotide comprising the nucleotide sequence of any oneof SEQ ID NOS:2 to 3431 in a polynucleotide comprising the nucleotidesequence represented by SEQ ID NO:1, and has an activity of regulatingan, expression of a polypeptide encoded by the polynucleotide. Specificexamples of the polynucleotide having an activity of regulating anexpression of a polypeptide encoded by the polynucleotide includes apolynucleotide encoding the above described EMF, such as a promoter, anoperator, an enhancer, a silencer, a ribosome-binding sequence, atranscriptional termination sequence, and the like.

The primer used for obtaining the ORF according to the above PCR cloningtechnique includes an oligonucleotide comprising a sequence which is thesame as a sequence of 10 to 200 continuous nucleotides in the nucleotidesequence of the ORF and an adjacent region or an oligonucleotidecomprising a sequence which is complementary to the oligonucleotide.Specific examples include an oligonucleotide comprising a sequence whichis the same as a sequence of 10 to 200 continuous nucleotides of thenucleotide sequence represented by any one of SEQ ID NOS:1 to 3431, andan oligonucleotide comprising a sequence complementary to theoligonucleotide comprising a sequence of at least 10 to 20 continuousnucleotide of any one of SEQ ID NOS:1 to 3431. When the primers are usedas a sense primer and an antisense primer, the above-describedoligonucleotides in which melting temperature (T_(m)) and the number ofnucleotides are not significantly different from each other arepreferred.

The oligonucleotide of the present invention includes an oligonucleotidecomprising a sequence which is the same as 10 to 200 continuousnucleotides of the nucleotide sequence represented by any one of SEQ IDNOS:1 to 3431 or an oligonucleotide comprising a sequence complementaryto the oligonucleotide.

Also, analogues of these oligonucleotides (hereinafter also referred toas “analogous oligonucleotides”) are also provided by the presentinvention and are useful in the methods described herein.

Examples of the analogous oligonucleotides include analogousoligonucleotides in which a phosphodiester bond in an oligonucleotide isconverted to a phosphorothioate bond, analogous oligonucleotides inwhich a phosphodiester bond in an oligonucleotide is converted to anN3′-P5′ phosphoamidate bond, analogous oligonucleotides in which riboseand a phosphodiester bond in an oligonucleotide is converted to apeptide nucleic acid bond, analogous oligonucleotides in which uracil inan oligonucleotide is replaced with C-5 propynyluracil, analogousoligonucleotides in which uracil in an oligonucleotide is replaced withC-5 thiazoluracil, analogous oligonucleotides in which cytosine in anoligonucleotide is replaced with C-5 propynylcytosine, analogousoligonucleotides in which cytosine in an oligonucleotide is replacedwith phenoxazine-modified cytosine, analogous oligonucleotides in whichribose in an oligonucleotide is replaced with 2′-O-propylribose,analogous oligonucleotides in which ribose in an oligonucleotide isreplaced with 2′-methoxyethoxyribose, and the like (Cell Engineering,16: 1463 (1997)).

The above oligonucleotides and analogous oligonucleotides of the presentinvention can be used as probes for hybridization and antisense nucleicacids described below in addition to as primers.

Examples of a primer for the antisense nucleic acid techniques known inthe art include an oligonucleotide which hybridizes the oligonucleotideof the present invention under stringent conditions and has an activityregulating expression of the polypeptide encoded by the polynucleotide,in addition to the above oligonucleotide.

3. Determination of Isozymes

Many mutants of coryneform bacteria which are useful in th production ofuseful substances, such as amino acids, nucleic acids, vitamins,saccharides, organic acids, and the like, are obtained by the presentinvention.

However, since the gene sequence data of the microorganism has been, todate, insufficient, useful mutants have been obtained by mutagenictechniques using a mutagen, such as nitrosoguanidine (NTG) or the like.

Although genes can be mutated randomly by the mutagenic method using theabove-described mutagen, all genes encoding respective isozymes havingsimilar properties relating to the metabolism of intermediates cannot bemutated. In the mutagenic method using a mutagen, genes are mutatedrandomly. Accordingly, harmful mutations worsening culturecharacteristics, such as delay in growth, accelerated foaming, and thelike, might be imparted at a great frequency, in a random manner.

However, if gene sequence information is available, such as is providedby the present invention, it is possible to mutate all of the genesencoding target isozymes. In this case, harmful mutations may be avoidedand the target mutation can be incorporated.

Namely, an accurate number and sequence information of the targetisozymes in coryneform bacteria can be obtained based on the ORF dataobtained in the above item 2. By using the sequence information, all ofthe target isozyme genes can be mutated into genes having the desiredproperties by, for example, the site-specific mutagenesis methoddescribed in Molecular Cloning, 2nd ed. to obtain useful mutants havingelevated productivity of useful substances.

4. Clarification or Determination of Biosynthesis Pathway and SignalTransmission Pathway

Attempts have been made to elucidate biosynthesis pathways and signaltransmission pathways in a number of organisms, and many findings havebeen reported. However, there are many unknown aspects of coryneformbacteria since a number of genes have not been identified so far.

These unknown points can be clarified by the following method.

The functional information of ORF derived from coryneform bacteria asidentified by the method of above item 2 is arranged. The term“arranged” means that the ORF is classified based on the biosynthesispathway of a substance or the signal transmission pathway to which theORF belongs using known information according to the functionalinformation. Next, the arranged ORF sequence information is comparedwith enzymes on the biosynthesis pathways or signal transmissionpathways of other known organisms. The resulting information is combinedwith known data on coryneform bacteria. Thus, the biosynthesis pathwaysand signal transmission pathways in coryneform bacteria, which have beenunknown so far, can be determined.

As a result that these pathways which have been unknown or unclearhitherto are clarified, a useful mutant for producing a target usefulsubstance can be efficiently obtained.

When the thus clarified pathway is judged as important in the synthesisof a useful product, a useful mutant can be obtained by selecting amutant wherein this pathway has been strengthened. Also, when the thusclarified pathway is judged as not important in the biosynthesis of thetarget useful product, a useful mutant can be obtained by selecting amutant wherein the utilization frequency of this pathway is lowered.

5. Clarification or Determination of Useful Mutation Point

Many useful mutants of coryneform bacteria which are suitable for theproduction of useful substances, such as amino acids, nucleic acids,vitamins, saccharides, organic acids, and the like, have been obtained.However, it is hardly known which mutation point is imparted to a geneto improve the productivity.

However, mutation points contained in production strains can beidentified by comparing desired sequences of the genome. DNA of theproduction strains obtained from coryneform bacteria by the mutagenictechnique with the nucleotide sequences of the corresponding genome DNAand ORF derived from coryneform bacteria determined by the methods ofthe above items 1 and 2 and analyzing them

Moreover, effective mutation points contributing to the production canbe easily specified from among these mutation points on the basis ofknown information relating to the metabolic pathways, the metabolicregulatory mechanisms, the structure activity correlation of enzymes,and the like.

When any efficient mutation can be hardly specified based on known data,the mutation points thus identified can be introduced into a wild strainof coryneform bacteria or a production strain free of the mutation.Then, it is examined whether or not any positive effect can be achievedon the production.

For example, by comparing the nucleotide sequence of homoserinedehydrogenase gene hom of a lysine-producing B-6-strain ofCorynebacterium glutamicum (Appl. Microbiol. Biotechnol., 32: 269-273(1989)) with the nucleotide sequence corresponding to the genome ofCorynebacterium glutamicum ATCC 13032 according to the presentinvention, a mutation of amino acid replacement in which valine at the59-position is replaced with alanine (Val59Ala) was identified. A strainobtained by introducing this mutation into the ATCC 13032 strain by thegene replacement method can produce lysine, which indicates that thismutation is an effective mutation contributing to the production oflysine.

Similarly, by comparing the nucleotide sequence of pyruvate carboxylasegene pyc of the B-6 strain with the nucleotide sequence corresponding tothe ATCC 13032 genome, a mutation of amino acid replacement in whichproline at the 458-position was replaced with serine (Pro458Ser) wasidentified. A strain obtained by introducing this mutation into alysine-producing strain of No. 58 (FERM BP-7134) of Corynebacteriumglutamicum free of this mutation shows an improved lysine productivityin comparison with the No. 58 strain, which indicates that this mutationis an effective mutation contributing to the production of lysine.

In addition, a mutation Ala213Thr in glucose-6-phosphate dehydrogenasewas specified as an effective mutation relating to the production oflysine by detecting glucose-6-phosphate dehydrogenase gene zwf of theB-6 strain.

Furthermore, the lysine-productivity of Corynebacterium glutamicum wasimproved by replacing the base at the 932-position of aspartokinase genelysC of the Corynebacterium glutamicum ATCC 13032 genome with cytosineto thereby replace threonine at the 311-position by isoleucine, whichindicates that this mutation is an effective mutation contributing tothe production of lysine.

Also, as another method to examine whether or not the identifiedmutation point is an effective mutation, there is a method in which themutation possessed by the lysine-producing strain is returned to thesequence of a wild type strain by the gene replacement method andwhether or not it has a negative influence on the lysine productivity.For example, when the amino acid replacement mutation Val59Ala possessedby hom of the lysine-producing B-6 strain was returned to a wild typeamino acid sequence, the lysine productivity was lowered in comparisonwith the B-6 strain. Thus, it was found that this mutation is aneffective mutation contributing to the production of lysine.

Effective mutation points can be more efficiently and comprehensivelyextracted by combining, if needed, the DNA array analysis or proteomeanalysis described below.

6. Method of Breeding Industrially Advantageous Production Strain

It has been a general practice to construct production strains, whichare used industrially in the fermentation production of the targetuseful substances, such as amino acids, nucleic acids, vitamins,saccharides, organic acids, and the like, by repeating mutagenesis andbreeding based on random mutagenesis using mutagens, such as NTG or thelike, and screening.

In recent years, many examples of improved production strains have beenmade through the use of recombinant DNA techniques. In breeding,however, most of the parent production strains to be improved aremutants obtained by a conventional mutagenic procedure (W.Leuchtenberger, Amino Acids—Technical Production and Use. In: Roehr (ed)Biotechnology, second edition, vol. 6, products of primary metabolism.VCH Verlagsgesellschaft mbH, Weinheim, P 465 (1996)).

Although mutagenesis methods have largely contributed to the progress ofthe fermentation industry, they suffer from a serious problem ofmultiple, random introduction of mutations into every part of thechromosome. Since many mutations are accumulated in a single chromosomeeach time a strain is improved, a production strain obtained by therandom mutation and selecting is generally inferior in properties (forexample, showing poor growth, delayed consumption of saccharides, andpoor resistance to stresses such as temperature and oxygen) to a wildtype strain, which brings about troubles such as failing to establish asufficiently elevated productivity, being frequently contaminated withmiscellaneous bacteria, requiring troublesome procedures in culturemaintenance, and the like, and, in its turn, elevating the productioncost in practice. In addition, the improvement in the productivity isbased on random mutations and thus the mechanism thereof is unclear.Therefore, it is very difficult to plan a rational breeding strategy forthe subsequent improvement in the productivity.

According to the present invention, effective mutation pointscontributing to the production can be efficiently specified from amongmany mutation points accumulated in the chromosome of a productionstrain which has been bred from coryneform bacteria and, therefore, anovel breeding method of assembling these effective mutations in thecoryneform bacteria can be established. Thus, a useful production straincan be reconstructed. It is also possible to construct a usefulproduction strain from a wild type strain.

Specifically, a useful mutant can be constructed in the followingmanner.

One of the mutation points is incorporated into a wild type strain ofcoryneform bacteria. Then, it is examined whether or not a positiveeffect is established on the production. When a positive effect isobtained, the mutation point is saved. When no effect is obtained, themutation point is removed. Subsequently, only a strain having theeffective mutation point is used as the parent strain, and the sameprocedure is repeated. In general, the effectiveness of a mutationpositioned upstream cannot be clearly evaluated in some cases when thereis a rate-determining point in the downstream of a biosynthesis pathway.It is therefore preferred to successively evaluate mutation pointsupward from downstream.

By reconstituting effective mutations by the method as described abovein a wild type strain or a strain which has a high growth speed or thesame ability to consume saccharides as the wild type strain, it ispossible to construct an industrially advantageous strain which is freeof troubles in the previous methods as described above and to conductfermentation production using such strains within a short time or at ahigher temperature.

For example, a lysine-producing mutant B-6 (Appl. Microbiol.Biotechnol., 32: 262-273 (1989)), which is obtained by multiple roundsof random mutagenesis from a wild type strain Corynebacterium glutamicumATCC 13032, enables lysine fermentation to be performed at a temperaturebetween 30 and 34° C. but shows lowered growth and lysine productivityat a temperature exceeding 34° C. Therefore, the fermentationtemperature should be maintained at 34° C. or lower. In contrastthereto, the production strain described in the above item 5, which isobtained by reconstituting effective mutations relating to lysineproduction, can achieve a productivity at 40 to 42° C. equal or superiorto the result obtained by culturing at 30 to 34° C. Therefore, thisstrain is industrially advantageous since it can save the load ofcooling during the fermentation.

When culture should be carried out at a high temperature exceeding 43°C., a production strain capable of conducting fermentation production ata high temperature exceeding 43° C. can be obtained by reconstitutinguseful mutations in a, microorganism belonging to the genusCorynebacterium which can grow at high temperature exceeding 43° C.Examples of the microorganism capable of growing at a high temperatureexceeding 43° C. include Corynebacterium thermoaminogenes, such asCorynebacterium thermoaminogenes FERM 9244, FERM 9245, FERM 9246 andFERM 9247.

A strain having a further improved productivity of the target productcan be obtained using the thus reconstructed strain as the parent strainand further breeding it using the conventional mutagenesis method, thegene amplification method, the gene replacement method using therecombinant DNA technique, the transduction method or the cell fusionmethod. Accordingly, the microorganism of the present inventionincludes, but is not limited to, a mutant, a cell fusion strain, atransformant, a transductant or a recombinant strain constructed byusing recombinant DNA techniques, so long as it is a producing strainobtained via the step of accumulating at least two effective mutationsin a coryneform bacteria in the course of breeding.

When a mutation point judged as being harmful to the growth orproduction is specified, on the other hand, it is examined whether ornot the producing strain used at present contains the mutation point.When it has the mutation, it can be returned to the wild type gene andthus a further useful production strain can be bred.

The breeding method as described above is applicable to microorganisms,other than coryneform bacteria, which have industrially advantageousproperties (for example, microorganisms capable of quickly utilizingless expensive carbon sources, microorganisms capable of growing athigher temperatures).

7. Production and Utilization of Polynucleotide Array

(1) Production of Polynucleotide Array

A polynucleotide array can be produced using the polynucleotide oroligonucleotide of the present invention obtained in the above items 1and 2.

Examples include a polynucleotide array comprising a, solid support towhich at least one of a polynucleotide comprising the nucleotidesequence represented by SEQ ID NOS:2 to 3501, a polynucleotide whichhybridizes with the polynucleotide under stringent conditions, and apolynucleotide comprising 10 to 200 continuous nucleotides in thenucleotide sequence of the polynucleotide is adhered; and apolynucleotide array comprising a solid support to which at least one ofa polynucleotide encoding a polypeptide comprising the amino acidsequence represented by any one of SEQ ID NOS:3502 to 7001, apolynucleotide which hybridizes with the polynucleotide under stringentconditions, and a polynucleotide comprising 10 to 200 continuous basesin the nucleotide sequences of the polynucleotides is adhered.

Polynucleotide arrays of the present invention include substrates knownin the art, such as a DNA chip, a DNA microarray and a DNA macroarray,and the like, and comprises a solid support and plural polynucleotidesor fragments thereof which are adhered to the surface of the solidsupport.

Examples of the solid support include a glass plate, a nylon membrane,and the like.

The polynucleotides or fragments thereof adhered to the surface of thesolid support can be adhered to the surface of the solid support usingthe general technique for preparing arrays. Namely, a method in whichthey are adhered to a chemically surface-treated solid support, forexample, to which a polycation such as polylysine or the like has beenadhered (Nat. Genet., 21: 15-19 (1999)). The chemically surface-treatedsupports are commercially available and the commercially available solidproduct can be used, as the solid support of the polynucleotide arrayaccording to the present invention.

As the polynucleotides or oligonucleotides adhered to the solid support,the polynucleotides and oligonucleotides of the present inventionobtained in the above items 1 and 2 can be used.

The analysis described below can be efficiently performed by adheringthe polynucleotides or oligonucleotides to the solid support at a highdensity, though a high fixation density is not always necessary.

Apparatus for achieving a high fixation density, such as an arrayerrobot or the like, is commercially available from Takara Shuzo (GMS417Arrayer), and the commercially available product can be used.

Also, the oligonucleotides of the present invention can be synthesizeddirectly on the solid support by the photolithography method or the like(Nat. Genet., 21: 20-24 (1999)). In this method, a linker having aprotective group which can be removed by light irradiation is firstadhered to a solid support, such as a slide glass or the like. Then, itis irradiated with light through a mask (a photolithograph mask)permeating light exclusively at a definite part of the adhesion part.Next, an oligonucleotide having a protective group which can be removedby light irradiation is added to the part. Thus, a ligation reactionwith the nucleotide arises exclusively at the irradiated part. Byrepeating this procedure, oligonucleotides, each having a desiredsequence, different from each other can be synthesized in respectiveparts. Usually, the oligonucleotides to be synthesized have a length of10 to 30 nucleotides.

(2) Use of Polynucleotide Array

The following procedures (a) and (b) can be carried out using thepolynucleotide array prepared in the above (1).

(a) Identification of Mutation Point of Coryneform Bacterium Mutant andAnalysis of Expression Amount and Expression Profile of Gene Encoded byGenome

By subjecting a gene derived from a mutant of coryneform bacteria or anexamined gene to the following steps (i) to (iv), the mutation point ofthe gene can be identified or the expression amount and expressionprofile of the gene can be analyzed:

-   (i) producing a polynucleotide array by the method of the above (1);-   (ii) incubating polynucleotides immobilized on the polynucleotide    array together with the labeled gene derived from a mutant of the    coryneform bacterium using the polynucleotide array produced in the    above (i) under hybridization conditions;-   (iii) detecting the hybridization; and-   (iv) analyzing the hybridization data.

The gene derived from a mutant of coryneform bacteria or the examinedgene include a gene relating to biosynthesis of at least one selectedfrom amino acids, nucleic acids, vitamins, saccharides, organic acids,and analogues thereof.

The method will be described in detail.

A single nucleotide polymorphism (SNP) in a human region of 2,300 kb hasbeen identified using polynucleotide arrays (Science, 280: 1077-82(1998)). In accordance with the method of identifying SNP and methodsdescribed in Science, 278: 680-686 (1997); Proc. Natl. Acad. Sci. USA,96: 12833-38 (1999); Science, 284: 1520-23 (1999), and the like usingthe polynucleotide array produced in the above (1) and a nucleic acidmolecule (DNA, RNA) derived from coryneform bacteria in the method ofthe hybridization, a mutation point of a useful mutant, which is usefulin producing an amino acid, a nucleic acid, a vitamin, a saccharide, anorganic acid, or the like can be identified and the gene expressionamount and the expression profile thereof can be analyzed.

The nucleic acid molecule (DNA, RNA) derived from the coryneformbacteria can be obtained according to the general method described inMolecular Cloning, 2nd ed. or the like. mRNA derived fromCorynebacterium glutamicum can also be obtained by the method of Bormannet al. (Molecular Microbiology, 6: 317-326 (1992)) or the like.

Although ribosomal RNA (rRNA) is usually obtained in large excess inaddition to the target mRNA, the analysis is not seriously disturbedthereby.

The resulting nucleic acid molecule derived from coryneform bacteria islabeled. Labeling can be carried out according to a method using afluorescent dye, a method using a radioisotope or the like.

Specific examples include a labeling method in which psoralen-biotin iscrosslinked with RNA extracted from a microorganism and, afterhybridization reaction, a fluorescent dye having streptoavidin boundthereto is bound to the biotin moiety (Nat. Biotechnol., 16: 45-48(1998)); a labeling method in which a reverse transcription reaction iscarried out using RNA extracted from a microorganism as a template andrandom primers as primers, and dUTP having a fluorescent dye (forexample, Cy3, Cy5) (manufactured by Amersham Pharmacia Biotech) isincorporated into cDNA (Proc. Natl. Acad. Sci. USA, 96: 12833-38(1999)); and the like.

The labeling specificity can be improved by replacing the random primersby sequences complementary to the 3′-end of ORF (J. Bacteriol., 181:6425-40 (1999)).

In the hybridization method, the hybridization and subsequent washingcan be carried out by the general method (Nat. Biotechnol., 14: 1675-80(1996), or the like).

Subsequently, the hybridization intensity is measured depending on thehybridization amount of the nucleic acid molecule used in the labeling.Thus, the mutation point can be identified and the expression amount ofthe gene can be calculated.

The hybridization intensity can be measured by visualizing thefluorescent signal, radioactivity, luminescence dose, and the like,using a laser confocal microscope, a CCD camera, a radiation imagingdevice (for example, STORM manufactured by Amersham Pharmacia Biotech),and the like, and then quantifying the thus visualized data.

A polynucleotide array on a solid support can also be analyzed andquantified using a commercially available apparatus, such as GMS418Array Scanner (manufactured by Takara Shuzo) or the like.

The gene expression amount can be analyzed using a commerciallyavailable software (for example, ImaGene manufactured by Takara Shuzo;Array Gauge manufactured by Fuji Photo Film; ImageQuant manufactured byAmersham Pharmacia Biotech, or the like).

A fluctuation in the expression amount of a specific gene can bemonitored using a nucleic acid molecule obtained in the time course ofculture as the nucleic acid molecule derived from coryneform bacteria.The culture conditions can be optimized by analyzing the fluctuation.

The expression profile of the microorganism at the total gene level(namely, which genes among a great number of genes encoded by the genomehave been expressed and the expression ratio thereof) can be determinedusing a nucleic acid molecule having the sequences of many genesdetermined from the full genome sequence of the microorganism. Thus, theexpression amount of the genes determined by the full genome sequencecan be analyzed and, in its turn, the biological conditions of themicroorganism can be recognized as the expression pattern at the fullgene level.

(b) Confirmation of the Presence of Gene Homologous to Examined Gene inCoryneform Bacteria

Whether or not a gene homologous to the examined gene, which is presentin an organism other than coryneform bacteria, is present in coryneformbacteria can be detected using the polynucleotide array prepared in theabove (1).

This detection can be carried out by a method in which an examined genewhich is present in an organism other than coryneform bacteria is usedinstead of the nucleic acid molecule derived from coryneform bacteriaused in the above identification/analysis method of (1).

8. Recording Medium Storing Full Genome Nucleotide Sequence and ORF Dataand Being Readable by a Computer and Methods for Using the Same

The term “recording medium or storage device which is readable by acomputer” means a recording medium or storage medium which can bedirectly readout and accessed with a computer. Examples include magneticrecording media, such as a floppy disk, a hard disk, a magnetic tape,and the like; optical recording media, such as CD-ROM, CD-R, CD-RW,DVD-ROM, DVD-RAM, DVD-RW, and the like; electric recording media, suchas RAM, ROM, and the like; and hybrids in these categories (for example,magnetic/optical recording media, such as MO and the like).

Instruments for recording or inputting in or on the recording medium orinstruments or devices for reading out the information in the recordingmedium can be appropriately selected, depending on the type of therecording medium and the access device utilized. Also, various dataprocessing programs, software, comparator and formats are used forrecording and utilizing the polynucleotide sequence information or thelike of the present invention in the recording medium. The informationcan be expressed in the form of a binary file, a text file or an ASCIIfile formatted with commercially available software, for example.Moreover, software for accessing the sequence information is availableand known to one of ordinary skill in the art.

Examples of the information to be recorded in the above-described mediuminclude the full genome nucleotide sequence information of coryneformbacteria as obtained in the above item 2, the nucleotide sequenceinformation of ORF, the amino acid sequence information encoded by theORF, and the functional information of polynucleotides coding for theamino acid sequences.

The recording medium or storage device which is readable by a computeraccording to the present invention refers to a medium in which theinformation of the present invention has been recorded. Examples includerecording media or storage devices which are readable by a computerstoring the nucleotide sequence information represented by SEQ ID NOS:1to 3501, the amino acid sequence information represented by SEQ IDNOS:3502 to 7001, the functional information of the nucleotide sequencesrepresented by SEQ ID NOS:1 to 3501, the functional information of theamino acid sequences represented by SEQ ID NOS:3502 to 7001, and theinformation listed in Table 1 below and the like.

9. System Based on a Computer Using the Recording Medium of the PresentInvention which is Readable by a Computer

The term “system based on a computer” as used herein refers a systemcomposed of hardware device(s) software device(s), and data recordingdevice(s) which are used for analyzing the data recorded in therecording medium of the present invention which is readable by acomputer.

The hardware device(s) are, for example, composed of an input unit, adata recording unit, a central processing unit and an output unitcollectively or individually.

By the software device(s), the data recorded in the recording medium ofthe present invention are searched or analyzed using the recorded dataand the hardware device(s) as described herein. Specifically, thesoftware device(s) contain at least one program which acts on or withthe system in order to screen, analyze or compare biologicallymeaningful structures or information from the nucleotide sequences,amino acid sequences and the like recorded in the recording mediumaccording to the present invention.

Examples of the software device(s) for identifying ORF and EMF domainsinclude GeneMark (Nuc. Acids. Res., 22: 4756-67 (1994)), GeneHacker(Protein, Nucleic Acid and Enzyme, 42: 3001-07 (1997)), Glimmer (TheInstitute of Genomic Research; Nuc. Acids. Res., 26: 544-548 (1998)) andthe like. In the process of using such a software device, the default(initial setting) parameters are usually used, although the parameterscan be changed, if necessary, in a manner known to one of ordinary skillin the art.

Examples of the software device(s) for identifying a genome domain or apolypeptide domain analogous to the target sequence or the targetstructural motif (homology searching) include FASTA, BLAST,Smith-Waterman, GenetyxMac (manufactured by Software Development), GCGPackage (manufactured by Genetic Computer Group), GenCore (manufacturedby Compugen), and the like. In the process of using such a softwaredevice, the default (initial setting) parameters are usually used,although the parameters can be changed, if necessary, in a manner knownto one of ordinary skill in the art.

Such a recording medium storing the full genome sequence data is usefulin preparing a polynucleotide array by which the expression amount of agene encoded by the genome DNA of coryneform bacteria and the expressionprofile at the total gene level of the microorganism, namely, whichgenes among many genes encoded by the genome have been expressed and theexpression ratio thereof, can be determined.

The data recording device(s) provided by the present invention are, forexample, memory device(s) for recording the data recorded in therecording medium of the present invention and target sequence or targetstructural motif data, or the like, and a memory accessing device(s) foraccessing the same.

Namely, the system based on a computer according to the presentinvention comprises the following:

-   (i) a user input device that inputs the information stored in the    recording medium of the present invention, and target sequence or    target structure motif information;-   (ii) a data storage device for at least temporarily storing the    input information;-   (iii) a comparator that compares the information stored in the    recording medium of the present invention with the target sequence    or target structure motif information, recorded by the data storing    device of (ii) for screening and analyzing nucleotide sequence    information which is coincident with or analogous to the target    sequence or target structure motif information; and-   (iv) an output device that shows a screening or analyzing result    obtained by the comparator.

This system is usable in the methods in items 2 to 5 as described abovefor searching and analyzing the ORF and EMF domains, target sequence,target structural motif, etc. of a coryneform bacterium, searchinghomologs, searching and analyzing isozymes, determining the biosynthesispathway and the signal transmission pathway, and identifying spots whichhave been found in the proteome analysis. The term “homologs” as usedherein includes both of orthologs and paralogs.

10. Production of Polypeptide Using ORF Derived from Coryneform Bacteria

The polypeptide of the present invention can be produced using apolynucleotide comprising the ORF obtained in the above item 2.Specifically, the polypeptide of the present invention can be producedby expressing the polynucleotide of the present invention or a fragmentthereof in a host cell, using the method described in Molecular Cloning,2nd ed., Current Protocols in Molecular Biology, and the like, forexample, according to the following method.

A DNA fragment having a suitable length containing a part encoding thepolypeptide is prepared from the full length ORF sequence, if necessary.

Also, DNA in which nucleotides in a nucleotide sequence at a partencoding the polypeptide of the present invention are replaced to give acodon suitable for expression of the host cell, if necessary. The DNA isuseful for efficiently producing the polypeptide of the presentinvention.

A recombinant vector is prepared by inserting the DNA fragment into thedownstream of a promoter in a suitable expression vector.

The recombinant vector is introduced to a host cell suitable for theexpression vector.

Any of bacteria, yeasts, animal cells, insect cells, plant cells, andthe like can be used as the host cell so long as it can be expressed inthe gene of interest.

Examples of the expression vector include those which can replicateautonomously in the above-described host cell or can be integrated intochromosome and have a promoter at such a position that the DNA encodingthe polypeptide of the present invention can be transcribed.

When a procaryote cell, such as a bacterium or the like, is used as thehost cell, it is preferred that the recombinant vector containing theDNA encoding the polypeptide of the present invention can replicateautonomously in the bacterium and is a recombinant vector constitutedby, at least a promoter, a ribosome binding sequence, the DNA of thepresent invention and a transcription termination sequence. A promotercontrolling gene can also be contained therewith in operablecombination.

Examples of the expression vectors include a vector plasmid which isreplicable in Corynebacterium glutamicum, such as pCG1 (JapanesePublished Unexamined Patent Application No. 134500/82), pCG2 (JapanesePublished Unexamined Patent Application No. 35197/83), pCG4 (JapanesePublished Unexamined Patent Application No. 183799/82), pCG11 (JapanesePublished Unexamined Patent Application No. 134500/82), pCG116, pCE54and pCB101 (Japanese Published Unexamined Patent Application No.105999/83), pCE51, pCE52 and pCE53 (Mol. Gen. Genet., 196: 175-178(1984)), and the like; a vector plasmid which is replicable inEscherichia coli, such as pET3 and pET11 (manufactured by Stratagene),pBAD, pThioHis and pTrcHis (manufactured by Invitrogen), pKK223-3 andpGEX2T (manufactured by Amersham Pharmacia Biotech), and the like; andpBTrp2, pBTac1 and pBTac2 (manufactured by Boehringer Mannheim Co.),pSE280 (manufactured by Invitrogen), pGEMEX-1 (manufactured by Promega),pQE-8 (manufactured by QIAGEN), pKYP10 (Japanese Published UnexaminedPatent Application No. 110600/83), pKYP200 (Agric. Biol. Chem., 48: 669(1984)), pLSA1 (Agric. Biol. Chem., 53: 277 (1989)), pGEL1 (Proc. Natl.Acad. Sci. USA, 82: 4306 (1985)), pBluescript II SK(−) (manufactured byStratagene), pTrs30 (prepared from Escherichia coli JM109/pTrS30 (FERMBP-5407)), pTrs32 (prepared from Escherichia coli JM109/pTrS32 (FERMBP-5408)), pGHA2 (prepared from Escherichia coli IGHA2 (FERM B-400),Japanese Published Unexamined Patent Application No. 221091/85), pGKA2(prepared from Escherichia coli IGKA2 (FERM BP-6798), Japanese PublishedUnexamined Patent Application No. 221091/85), pTerm2 (U.S. Pat. Nos.4,686,191, 4,939,094 and 5,160,735), pSupex, pUB110, pTP5, pC194 andpEG400 (J. Bacteriol., 172: 2392 (1990)), pGEX (manufactured byPharmacia), pET system (manufactured by Novagen), and the like.

Any promoter can be used so long as it can function in the host cell.Examples include promoters derived from Escherichia coli, phage and thelike, such as trp promoter (P_(trp)), lac promoter, P_(L) promoter,P_(R) promoter, T7 promoter and the like. Also, artificially designedand modified promoters, such as a promoter in which two Ptrp are linkedin series (P_(trp)×2), tac promoter, lacT7 promoter letI promoter andthe like, can be used.

It is preferred to use a plasmid in which the space betweenShine-Dalgarno sequence which is the ribosome binding sequence and theinitiation codon is adjusted to an appropriate distance (for example, 6to 18 nucleotides).

The transcription termination sequence is not always necessary for theexpression of the DNA of the present invention. However, it is preferredto arrange the transcription terminating sequence at just downstream ofthe structural gene.

One of ordinary skill in the art will appreciate that the codons of theabove-described elements may be optimized, in a known manner, dependingon the host cells and environmental conditions utilized.

Examples of the host cell include microorganisms belonging to the genusEscherichia, the genus Serratia, the genus Bacillus, the genusBrevibacterium, the genus Corynebacterium, the genus Microbacterium, thegenus Pseudomonas, and the like. Specific examples include Escherichiacoli XL1-Blue, Escherichia coli XL2-Blue, Escherichia coli DH1,Escherichia coli MC1000, Escherichia coli KY3276, Escherichia coliW1485; Escherichia coli JM109, Escherichia coli HB101, Escherichia coliNo. 49, Escherichia coli W3110, Escherichia coli NY49, Escherichia coliG1698, Escherichia coli TB1, Serratia ficaria, Serratia fonticola,Serratia liquefaciens, Serratia marcescens, Bacillus subtilis, Bacillusamyloliquefaciens, Corynebacterium ammoniagenes, Brevibacteriumimmariophilum ATCC 14068, Brevibacterium saccharolyticum ATCC 14066,Corynebacterium glutamicum ATCC 13032, Corynebacterium glutamicum ATCC13869, Corynebacterium glutamicum ATCC 14067 (prior genus and species:Brevibacterium flavum), Corynebacterium glutamicum ATCC 13869 (priorgenus and species: Brevibacterium lactofermentum, or Corynebacteriumlactofermentum), Corynebacterium acetoacidophilum ATCC 13870,Corynebacterium thermoaminogenes FERM 9244, Microbacterium ammoniaphilumATCC 15354, Pseudomonas putida, Pseudomonas sp. D-0110, and the like.

When Corynebacterium glutamicum or an analogous microorganism is used asa host, an EMF necessary for expressing the polypeptide is not alwayscontained in the vector so long as the polynucleotide of the presentinvention contains an EMF. When the EMF is not contained in thepolynucleotide, it is necessary to prepare the EMF separately and ligateit so as to be in operable combination. Also, when a higher expressionamount or specific expression regulation is necessary, it is necessaryto ligate the EMF corresponding thereto so as to put the EMF in operablecombination with the polynucleotide. Examples of using an externallyligated EMF are disclosed in Microbiology, 142: 1297-1309 (1996).

With regard to the method for the introduction of the recombinantvector, any method for introducing DNA into the above-described hostcells, such as a method in which a calcium ion is used (Proc. Natl.Acad. Sci. USA, 69: 2110 (1972)), a protoplast method (JapanesePublished Unexamined Patent Application No. 2483942/88), the methodsdescribed in Gene, 17: 107 (1982) and Molecular & General Genetics, 168:111 (1979) and the like, can be used.

When yeast is used as the host cell, examples of the expression vectorinclude pYES2 (manufactured by Invitrogen), YEp13 (ATCC 37115), YEp24(ATCC 37051), YCp50 (ATCC 37419), pHS19, pHS15, and the like.

Any promoter can be used so long as it can be expressed in yeast.Examples include a promoter of a gene in the glycolytic pathway, such ashexose kinase and the like, PHO5 promoter, PGK promoter, GAP promoter,ADH promoter, gal 1 promoter, gal 10 promoter, a heat shock proteinpromoter, MF α1 promoter, CUP 1 promoter, and the like.

Examples of the host cell include microorganisms belonging to the genusSaccharomyces, the genus Schizosaccharomyces, the genus Kluyveromyces,the genus Trichosporon, the genus Schwanniomyces, the genus Pichia, thegenus Candida and the like. Specific examples include Saccharomycescerevisiae, Schizosaccharomyces pombe, Kluyveromyces lactis,Trichosporon pullulans, Schwanniomyces alluvius, Candida utilis and thelike.

With regard to the method for the introduction of the recombinantvector, any method for introducing DNA into yeast, such as anelectroporation method (Methods. Enzymol., 194: 182 (1990)), aspheroplast method (Proc. Natl. Acad. Sci. USA, 75: 1929 (1978)), alithium acetate method (J. Bacteriol., 153: 163 (1983)), a methoddescribed in Proc. Natl. Acad. Sci. USA, 75: 1929 (1978) and the like,can be used.

When animal cells are used as the host cells, examples of the expressionvector include pcDNA3.1, pSinRep5 and pCEP4 (manufactured byInvitorogen), pRev-Tre (manufactured by Clontech), pAxCAwt (manufacturedby Takara Shuzo), pcDNAI and pcDM8 (manufactured by Funakoshi), pAGE107(Japanese Published Unexamined Patent Application No. 22979/91;Cytotechnology, 3:133 (1990)), pAS3-3 (Japanese Published UnexaminedPatent Application No. 227075/90), pcDM8 (Nature, 329: 840 (1987)),pcDNAI/Amp (manufactured by Invitrogen), pREP4 (manufactured byInvitrogen), pAGE103 (J. Biochem., 101: 1307 (1987)), pAGE210, and thelike.

Any promoter can be used so long as it can function in animal cells.Examples include a promoter of IE (immediate early) gene ofcytomegalovirus (CMV), an early promoter of SV40, a promoter ofretrovirus, a metallothionein promoter, a heat shock promoter, SRαpromoter, and the like. Also, the enhancer of the IE gene of human CMVcan be used together with the promoter.

Examples of the host cell include human Namalwa cell, monkey COS cell,Chinese hamster CHO cell, HST5637 (Japanese Published Unexamined PatentApplication No. 299/88), and the like.

The method for introduction of the recombinant vector into animal cellsis not particularly limited, so long as it is the general method forintroducing DNA into animal cells, such as an electroporation method(Cytotechnology, 3: 133 (1990)), a calcium phosphate method (JapanesePublished Unexamined Patent Application No. 227075/90), a lipofectionmethod (Proc. Natl. Acad. Sci. USA, 84, 7413 (1987)), the methoddescribed in Virology, 52: 456 (1973), and the like.

When insect cells are used as the host cells, the polypeptide can beexpressed, for example, by the method described in BacurovirusExpression Vectors, A Laboratory Manual, W.H. Freeman and Company, NewYork (1992), Bio/Technology, 6: 47 (1988), or the like.

Specifically, a recombinant gene transfer vector and bacurovirus aresimultaneously inserted into insect cells to obtain a recombinant virusin an insect cell culture supernatant, and then the insect cells areinfected with the resulting recombinant virus to express thepolypeptide.

Examples of the gene introducing vector used in the method includepBlueBac4.5, pVL1392, pVL1393 and pBlueBacIII (manufactured byInvitrogen), and the like.

Examples of the bacurovirus include Autographa californica nuclearpolyhedrosis virus with which insects of the family Barathra areinfected, and the like.

Examples of the insect cells include Spodoptera frugiperda oocytes Sf9and Sf21 (Bacurovirus Expression Vectors, A Laboratory Manual, W.H.Freeman and Company, New York (1992)), Trichoplusia ni oocyte High 5(manufactured by Invitrogen) and the like.

The method for simultaneously incorporating the above-describedrecombinant gene transfer vector and the above-described bacurovirus forthe preparation of the recombinant virus include calcium phosphatemethod (Japanese Published Unexamined Patent Application No. 227075/90),lipofection method (Proc. Natl. Acad. Sci. USA, 84: 7413 (1987)) and thelike.

When plant cells are used as the host cells, examples of expressionvector include a Ti plasmid, a tobacco mosaic virus vector, and thelike.

Any promoter can be used so long as it can be expressed in plant cells.Examples include 35S promoter of cauliflower mosaic virus (CaMV), riceactin 1 promoter, and the like.

Examples of the host cells include plant cells and the like, such astobacco, potato, tomato, carrot, soybean, rape, alfalfa, rice, wheat,barley, and the like.

The method for introducing the recombinant vector is not particularlylimited, so long as it is the general method for introducing DNA intoplant cells, such as the Agrobacterium method (Japanese PublishedUnexamined Patent Application No. 140885/84, Japanese PublishedUnexamined Patent Application No. 70080/85, WO 94/00977), theelectroporation method (Japanese Published Unexamined PatentApplication, No. 251887/85), the particle gun method (Japanese Patents2606856 and 2517813), and the like.

The transformant of the present invention includes a transformantcontaining the polypeptide of the present invention per se rather thanas a recombinant vector, that is, a transformant containing thepolypeptide of the present invention which is integrated into achromosome of the host, in addition to the transformant containing theabove recombinant vector.

When expressed in yeasts, animal cells, insect cells or plant cells, aglycopolypeptide or glycosylated polypeptide can be obtained.

The polypeptide can be produced by culturing the thus obtainedtransformant of the present invention in a culture medium to produce andaccumulate the polypeptide of the present invention or any polypeptideexpressed under the control of an EMF of the present invention, andrecovering the polypeptide from the culture.

Culturing of the transformant of the present invention in a culturemedium is carried out according to the conventional method as used inculturing of the host.

When the transformant of the present invention is obtained using aprokaryote, such as Escherichia coli or the like, or a eukaryote, suchas yeast or the like, as the host, the transformant is cultured.

Any of a natural medium and a synthetic medium can be used, so long asit contains a carbon source, a nitrogen source, an inorganic salt andthe like which can be assimilated by the transformant and can performculturing of the transformant efficiently.

Examples of the carbon source include those which can be assimilated bythe transformant, such as carbohydrates (for example, glucose, fructose,sucrose, molasses containing them, starch, starch hydrolysate, and thelike), organic acids (for example, acetic acid, propionic acid, and thelike), and alcohols (for example, ethanol, propanol, and the like).

Examples of the nitrogen source include ammonia, various ammonium saltsof inorganic acids or organic acids (for example, ammonium chloride,ammonium sulfate, ammonium acetate, ammonium phosphate, and the like),other nitrogen-containing compounds, peptone, meat extract, yeastextract, corn steep liquor, casein hydrolysate, soybean meal and soybeanmeal hydrolysate, various fermented cells and hydrolysates thereof, andthe like.

Examples of inorganic salt include potassium dihydrogen phosphate,dipotassium hydrogen phosphate, magnesium phosphate, magnesium sulfate,sodium chloride, ferrous sulfate, manganese sulfate, copper sulfate,calcium carbonate, and the like.

The culturing is carried out under aerobic conditions by shakingculture, submerged-aeration stirring culture or the like. The culturingtemperature is preferably from 15 to 40° C., and the culturing time isgenerally from 16 hours to 7 days. The pH of the medium is preferablymaintained at 3.0 to 9.0 during the culturing. The pH can be adjustedusing an inorganic or organic acid, an alkali solution, urea, calciumcarbonate, ammonia, or the like.

Also, antibiotics, such as ampicillin, tetracycline, and the like, canbe added to the medium during the culturing, if necessary.

When a microorganism transformed with a recombinant vector containing aninducible promoter is cultured, an inducer can be added to the medium,if necessary.

For example, isopropyl-β-D-thiogalactopyranoside (IPTG) or the like canbe added to the medium when a microorganism transformed with arecombinant vector containing lac promoter is cultured, or indoleacrylicacid (IAA) or the like can by added thereto when a microorganismtransformed with an expression vector containing trp promoter iscultured.

Examples of the medium used in culturing a transformant obtained usinganimal cells as the host cells include RPMI 1640 medium (The Journal ofthe American Medical Association, 199: 519 (1967)), Eagle's MEM medium(Science, 122: 501 (1952)), Dulbecco's modified MEM medium (Virology, 8,396 (1959)), 199 Medium (Proceeding of the Society for the BiologicalMedicine, 73:1 (1950)), the above-described media to which fetal calfserum has been added, and the like.

The culturing is carried out generally at a pH of 6 to 8 and atemperature of 30 to 40° C. in the presence of 5% CO₂ for 1 to 7 days.

Also, if necessary, antibiotics, such as kanamycin, penicillin, and thelike, can be added to the medium during the culturing.

Examples of the medium used in culturing a transformant obtained usinginsect cells as the host cells include TNM-FH medium (manufactured byPharmingen), Sf-900 II SFM (manufactured by Life Technologies), ExCell400 and ExCell 405 (manufactured by JRH Biosciences), Grace's InsectMedium (Nature, 195: 788 (1962)), and the like.

The culturing is carried out generally at a pH of 6 to 7 and atemperature of 25 to 30° C. for 1 to 5 days.

Additionally, antibiotics, such as gentamicin and the like, can be addedto the medium during the culturing, if necessary.

A transformant obtained by using a plant cell as the host cell can beused as the cell or after differentiating to a plant cell or organ.Examples of the medium used in the culturing of the transformant includeMurashige and Skoog (MS) medium, White medium, media to which a planthormone, such as auxin, cytokinine, or the like has been added, and thelike.

The culturing is carried out generally at a pH of 5 to 9 and atemperature of 20 to 40° C. for 3 to 60 days.

Also, antibiotics, such as kanamycin, hygromycin and the like, can beadded to the medium during the culturing, if necessary.

As described above, the polypeptide can be produced by culturing atransformant derived from a microorganism, animal cell or plant cellcontaining a recombinant vector to which a DNA encoding the polypeptideof the present invention has been inserted according to the generalculturing method to produce and accumulate the polypeptide, andrecovering the polypeptide from the culture.

The process of gene expression may include secretion of the encodedprotein production or fusion protein expression and the like inaccordance with the methods described in Molecular Cloning, 2nd ed., inaddition to direct expression.

The method for producing the polypeptide of the present inventionincludes a method of intracellular expression in a host cell, a methodof extracellular secretion from a host cell, or a method of productionon a host cell membrane outer envelope. The method can be selected bychanging the host cell employed or the structure of the polypeptideproduced.

When the polypeptide of the present invention is produced in a host cellor on a host cell membrane outer envelope, the polypeptide can bepositively secreted extracellularly according to, for example, themethod of Paulson et al. (J. Biol. Chem., 264: 17619 (1989)), the methodof Lowe et al. (Proc. Natl. Acad. Sci. USA, 86: 8227 (1989); GenesDevelop., 4: 1288 (1990)), and/or the methods described in JapanesePublished Unexamined Patent Application No. 336963/93, WO 94/23021, andthe like.

Specifically, the polypeptide of the present invention can be positivelysecreted extracellularly by expressing it in the form that a signalpeptide has been added to the foreground of a polypeptide containing anactive site of the polypeptide of the present invention according to therecombinant DNA technique.

Furthermore, the amount produced can be increased using a geneamplification system, such as by use of a dihydrofolate reductase geneor the like according to the method described in Japanese PublishedUnexamined Patent Application No. 227075/90.

Moreover, the polypeptide of the present invention can be produced by atransgenic animal individual (transgenic nonhuman animal) or plantindividual (transgenic plant).

When the transformant is the animal individual or plant individual, thepolypeptide of the present invention can be produced by breeding orcultivating it so as to produce and accumulate the polypeptide, andrecovering the polypeptide from the animal individual or plantindividual.

Examples of the method for producing the polypeptide of the presentinvention using the animal individual include a method for producing thepolypeptide of the present invention in an animal developed by insertinga gene according to methods known to those of ordinary skill in the art(American Journal of Clinical Nutrition, 63: 639S (1996), AmericanJournal of Clinical Nutrition, 63: 627S (1996), Bio/Technology, 9: 830(1991)).

In the animal individual, the polypeptide can be produced by breeding atransgenic nonhuman animal to which the DNA encoding the polypeptide ofthe present invention has been inserted to produce and accumulate thepolypeptide in the animal, and recovering the polypeptide from theanimal. Examples of the production and accumulation place in the animalinclude milk (Japanese Published Unexamined Patent Application No.309192/88), egg and the like of the animal. Any promoter can be used, solong as it can be expressed in the animal. Suitable examples include anα-casein promoter, a β-casein promoter, a β-lactoglobulin promoter, awhey acidic protein promoter, and the like, which are specific formammary glandular cells.

Examples of the method for producing the polypeptide of the presentinvention using the plant individual include a method for producing thepolypeptide of the present invention by cultivating a transgenic plantto which the DNA encoding the protein of the present invention by aknown method (Tissue Culture, 20 (1994), Tissue Culture, 21 (1994),Trends in Biotechnology, 15: 45 (1997)) to produce and accumulate thepolypeptide in the plant, and recovering the polypeptide from the plant.

The polypeptide according to the present invention can also be obtainedby translation in vitro.

The polypeptide of the present invention can be produced by atranslation system in vitro. There are, for example, two in vitrotranslation methods which may be used, namely, a method using RNA as atemplate and another method using DNA as a template. The template RNAincludes the whole RNA, mRNA, an in vitro transcription product, and thelike. The template DNA includes a plasmid containing a transcriptionalpromoter and a target gene integrated therein and downstream of theinitiation site, a PCR/RT-PCR product and the like. To select the mostsuitable system for the in vitro translation, the origin of the geneencoding the protein to be synthesized (prokaryotic cell/eucaryoticcell), the type of the template (DNA/RNA), the purpose of using thesynthesized protein and the like should be considered. In vitrotranslation kits having various characteristics are commerciallyavailable from many companies (Boehringer Mannheim, Promega, Stratagene,or the like), and every kit can be used in producing the polypeptideaccording to the present invention.

Transcription/translation of a DNA nucleotide sequence cloned into aplasmid containing a T7 promoter can be carried out using an in vitrotranscription/translation system E. coli T7 S30 Extract System forCircular DNA (manufactured by Promega, catalogue No. L1130). Also,transcription/translation using, as a template, a linear prokaryotic DNAof a supercoil non-sensitive promoter, such as lacUV5, tac, λPL(con),λPL, or the like, can be carried out using an in vitrotranscription/translation system E. coli S30 Extract System for LinearTemplates (manufactured by Promega, catalogue No. L1030). Examples ofthe linear prokaryotic DNA used as a template include a DNA fragment, aPCR-amplified DNA product, a duplicated oligonucleotide ligation, an invitro transcriptional RNA, a prokaryotic RNA, and the like.

In addition to the production of the polypeptide according to thepresent invention, synthesis of a radioactive labeled protein,confirmation of the expression capability of a cloned gene, analysis ofthe function of transcriptional reaction or translation reaction, andthe like can be carried out using this system.

The polypeptide produced by the transformant of the present inventioncan be isolated and purified using the general method for isolating andpurifying an enzyme. For example, when the polypeptide of the presentinvention is expressed as a soluble product in the host cells, the cellsare collected by centrifugation after cultivation, suspended in anaqueous buffer, and disrupted using an ultrasonicator, a French press, aManton Gaulin homogenizer, a Dynomill, or the like to obtain a cell-freeextract. From the supernatant obtained by centrifuging the cell-freeextract, a purified product can be obtained by the general method usedfor isolating and purifying an enzyme, for example, solvent extraction,salting out using ammonium sulfate or the like, desalting, precipitationusing an organic solvent, anion exchange chromatography using a resin,such as diethylaminoethyl (DEAE)-Sepharose, DIAION HPA-75 (manufacturedby Mitsubishi Chemical) or the like, cation exchange chromatographyusing a resin, such as S-Sepharose FF (manufactured by Pharmacia) or thelike, hydrophobic chromatography using a resin, such as butyl sepharose,phenyl sepharose or the like, gel filtration using a molecular sieve,affinity chromatography, chromatofocusing, or electrophoresis, such asisoelectronic focusing or the like, alone or in combination thereof.

When the polypeptide is expressed as an insoluble product in the hostcells, the cells are collected in the same manner, disrupted andcentrifuged to recover the insoluble product of the polypeptide as theprecipitate fraction. Next, the insoluble product of the polypeptide issolubilized with a protein denaturing agent. The solubilized solution isdiluted or dialyzed to lower the concentration of the protein denaturingagent in the solution. Thus, the normal configuration of the polypeptideis reconstituted. After the procedure, a purified product of thepolypeptide can be obtained by a purification/isolation method similarto the above.

When the polypeptide of the present invention or its derivative (forexample, a polypeptide formed by adding a sugar chain thereto) issecreted out of cells, the polypeptide or its derivative can becollected in the culture supernatant. Namely, the culture supernatant isobtained by treating the culture medium in a treatment similar to theabove (for example, centrifugation). Then, a purified product can beobtained from the culture medium using a purification/isolation methodsimilar to the above.

The polypeptide obtained by the above method is within the scope of thepolypeptide of the present invention, and examples include a polypeptideencoded by a polynucleotide comprising the nucleotide sequence selectedfrom SEQ ID NOS:2 to 3431, and a polypeptide comprising an amino acidsequence represented by any one of SEQ ID NOS:3502 to 6931.

Furthermore, a polypeptide comprising an amino acid sequence in which atleast one amino acids is deleted, replaced, inserted or added in theamino acid sequence of the polypeptide and having substantially the sameactivity as that of the polypeptide is included in the scope of thepresent invention. The term “substantially the same activity as that ofthe polypeptide” means the same activity represented by the inherentfunction, enzyme activity or the like possessed by the polypeptide whichhas not been deleted, replaced, inserted or added. The polypeptide canbe obtained using a method for introducing part-specific mutation(s)described in, for example, Molecular Cloning, 2nd ed., Current Protocolsin Molecular Biology, Nuc. Acids. Res., 10: 6487 (1982), Proc. Natl.Acad. Sci. USA, 79: 6409 (1982), Gene, 34: 315 (1985), Nuc. Acids. Res.,13: 4431 (1985), Proc. Natl. Acad. Sci. USA, 82: 488 (1985) and thelike. For example, the polypeptide can be obtained by introducingmutation(s) to DNA encoding a polypeptide having the amino acid sequencerepresented by any one of SEQ ID NOS:3502 to 6931. The number of theamino acids which are deleted, replaced, inserted or added is notparticularly limited; however, it is usually 1 to the order of tens,preferably 1 to 20, more preferably 1 to 10, and most preferably 1 to 5,amino acids.

The at least one amino acid deletion, replacement, insertion or additionin the amino acid sequence of the polypeptide of the present inventionis used herein to refer to that at least one amino acid is deleted,replaced, inserted or added to at one or plural positions in the aminoacid sequence. The deletion, replacement, insertion or addition may becaused in the same amino acid sequence simultaneously. Also, the aminoacid residue replaced, inserted or added can be natural or non-natural.Examples of the natural amino acid residue include L-alanine,L-asparagine, L-asparatic acid, L-glutamine, L-glutamic acid, glycine,L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine,L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan,L-tyrosine, L-valine, L-cysteine, and the like.

Herein, examples of amino acid residues which are replaced with eachother are shown below. The amino acid residues in the same group can bereplaced with each other.

Group A:

leucine, isoleucine, norleucine, valine, norvaline, alanine,2-aminobutanoic acid, methionine, O-methylserine, t-butylglycine,t-butylalanine, cyclohexylalanine;

Group B:

asparatic acid, glutamic acid, isoasparatic acid, isoglutamic acid,2-aminoadipic acid, 2-aminosuberic acid;

Group C:

asparagine, glutamine;

Group D:

lysine, arginine, ornithine, 2,4-diaminobutanoic acid,2,3-diaminopropionic acid;

Group E:

proline, 3-hydroxyproline, 4-hydroxyproline;

Group F:

serine, threonine, homoserine;

Group G:

phenylalanine, tyrosine.

Also, in order that the resulting mutant polypeptide has substantiallythe same activity as that of the polypeptide which has not been mutated,it is preferred that the mutant polypeptide has a homology of 60% ormore, preferably 80% or more, and particularly preferably 95% or more,with the polypeptide which has not been mutated, when calculated, forexample, using default (initial setting) parameters by a homologysearching software, such as BLAST, FASTA, or the like.

Also, the polypeptide of the present invention can be produced by achemical synthesis method, such as Fmoc (fluorenylmethyloxycarbonyl)method, tBoc (t-butyloxycarbonyl) method, or the like. It can also besynthesized using a peptide synthesizer manufactured by AdvancedChemTech, Perkin-Elmer, Pharmacia, Protein Technology Instrument,Synthecell-Vega, PerSeptive, Shimadzu Corporation, or the like.

The transformant of the present invention can be used for objects otherthan the production of the polypeptide of the present invention.

Specifically, at least one component selected from an amino acid, anucleic acid, a vitamin, a saccharide, an organic acid, and analoguesthereof can be produced by culturing the transformant containing thepolynucleotide or recombinant vector of the present invention in amedium to produce and accumulate at least one component selected fromamino acids, nucleic acids, vitamins, saccharides, organic acids, andanalogues thereof, and recovering the same from the medium.

The biosynthesis pathways, decomposition pathways and regulatorymechanisms of physiologically active substances such as amino acids,nucleic acids, vitamins, saccharides, organic acids and analoguesthereof differ from organism to organism. The productivity of such aphysiologically active substance can be improved using thesedifferences, specifically by introducing a heterogeneous gene relatingto the biosynthesis thereof. For example, the content of lysine, whichis one of the essential amino acids, in a plant seed was improved byintroducing a synthase gene derived from a bacterium (WO 93/19190).Also, arginine is excessively produced in a culture by introducing anarginine synthase gene derived from Escherichia coli (Japanese ExaminedPatent Publication 23750/93).

To produce such a physiologically active substance, the transformantaccording to the present invention can be cultured by the same method asemployed in culturing the transformant for producing the polypeptide ofthe present invention as described above. Also, the physiologicallyactive substance can be recovered from the culture medium in combinationwith, for example, the ion exchange resin method, the precipitationmethod and other known methods.

Examples of methods known to one of ordinary skill in the art includeelectroporation, calcium transfection, the protoplast method, the methodusing a phage, and the like, when the host is a bacterium; andmicroinjection, calcium phosphate transfection, the positively chargedlipid-mediated method and the method using a virus, and the like, whenthe host is a eukaryote (Molecular Cloning, 2nd. ed.; Spector et al.,Cells/a laboratory manual, Cold Spring Harbour Laboratory Press, 1998)).Examples of the host include prokaryotes, lower eukaryotes (for example,yeasts), higher eukaryotes (for example, mammals), and cells isolatedtherefrom. As the state of a recombinant polynucleotide fragment presentin the host cells, it can be integrated into the chromosome of the host.Alternatively, it can be integrated into a factor (for example, aplasmid) having an independent replication unit outside the chromosome.These transformants are usable in producing the polypeptides of thepresent invention encoded by the ORF of the genome of Corynebacteriumglutamicum, the polynucleotides of the present invention and fragmentsthereof. Alternatively, they can be used in producing arbitrarypolypeptides under the regulation by an EMF of the present invention.

11. Preparation of Antibody Recognizing the Polypeptide of the PresentInvention

An antibody which recognizes the polypeptide of the present invention,such as a polyclonal antibody, a monoclonal antibody, or the like, canbe produced using, as an antigen, a purified product of the polypeptideof the present invention or a partial fragment polypeptide of thepolypeptide or a peptide having a partial amino acid sequence of thepolypeptide of the present invention.

(1) Production of Polyclonal Antibody

A polyclonal antibody can be produced using, as an antigen, a purifiedproduct of the polypeptide of the present invention, a partial fragmentpolypeptide of the polypeptide, or a peptide having a partial amino acidsequence of the polypeptide of the present invention, and immunizing ananimal with the same.

Examples of the animal to be immunized include rabbits, goats, rats,mice, hamsters, chickens and the like.

A dosage of the antigen is preferably 50 to 100 μg per animal.

When the peptide is used as the antigen, it is preferably a peptidecovalently bonded to a carrier protein, such as keyhole limpethaemocyanin, bovine thyroglobulin, or the like. The peptide used as theantigen can be synthesized by a peptide synthesizer.

The administration of the antigen is, for example, carried out 3 to 10times at the intervals of 1 or 2 weeks after the first administration.On the 3rd to 7th day after each administration, a blood sample iscollected from the venous plexus of the eyeground, and it is confirmedthat the serum reacts with the antigen by the enzyme immunoassay(Enzyme-linked Immunosorbent Assay (ELISA), Igaku Shoin (1976);Antibodies—A Laboratory Manual, Cold Spring Harbor Laboratory (1988)) orthe like.

Serum is obtained from the immunized non-human mammal with a sufficientantibody titer against the antigen used for the immunization, and theserum is isolated and purified to obtain a polyclonal antibody.

Examples of the method for the isolation and purification includecentrifugation, salting out by 40-50% saturated ammonium sulfate,caprylic acid precipitation (Antibodies, A Laboratory manual, ColdSpring Harbor Laboratory (1988)), or chromatography using aDEAE-Sepharose column, an anion exchange column, a protein A- orG-column, a gel filtration column, and the like, alone or in combinationthereof, by methods known to those of ordinary skill in the art.

(2) Production of Monoclonal Antibody

(a) Preparation of Antibody-Producing Cell

A rat having a serum showing an enough antibody titer against a partialfragment polypeptide of the polypeptide of the present invention usedfor immunization is used as a supply source of an antibody-producingcell.

On the 3rd to 7th day after the antigen substance is finallyadministered the rat showing the antibody titer, the spleen is excised.

The spleen is cut to pieces in MEM medium (manufactured by NissuiPharmaceutical), loosened using a pair of forceps, followed bycentrifugation at 1,200 rpm for 5 minutes, and the resulting supernatantis discarded.

The spleen in the precipitated fraction is treated with a Tris-ammoniumchloride buffer (pH 7.65) for 1 to 2 minutes to eliminate erythrocytesand washed three times with MEM medium, and the resulting spleen cellsare used as antibody-producing cells.

(b) Preparation of Myeloma Cells

As myeloma cells, an established cell line obtained from mouse or rat isused. Examples of useful cell lines include those derived from a mouse,such as P3-X63Ag8-U1 (hereinafter referred to as “UP3-U1”) (Curr. Topicsin Microbiol. Immunol., 81: 1 (1978); Europ. J. Immunol., 6: 511(1976)); SP2/O-Ag14 (SP-2) (Nature, 276: 269 (1978)): P3-X63-Ag8653(653) (J. Immunol, 123: 1548 (1979)); P3-X63-Ag8 (X63) cell line(Nature, 256: 495 (1975)), and the like, which are8-azaguanine-resistant mouse (BALB/c) myeloma cell lines. These celllines are subcultured in 8-azaguanine medium (medium in which, to amedium obtained by adding. 1.5 mmol/l glutamine, 5×10⁻⁵ mol/l2-mercaptoethanol, 10 μg/ml gentamicin and 10% fetal calf serum (FCS)(manufactured by CSL) to RPMI-1640 medium (hereinafter referred to asthe “normal medium”), 8-azaguanine is further added at 15 μg/ml) andcultured in the normal medium 3 or 4 days before cell fusion, and 2×10⁷or more of the cells are used for the fusion.

(c) Production of Hybridoma

The antibody-producing cells obtained in (a) and the myeloma cellsobtained in (b) are washed with MEM medium or PBS (disodium hydrogenphosphate: 1.83 g, sodium dihydrogen phosphate: 0.21 g, sodium chloride:7.65 g, distilled water: 1 liter, pH: 7.2) and mixed to give a ratio ofantibody-producing cells:myeloma cells=5:1 to 10:1, followed bycentrifugation at 1,200 rpm for 5 minutes, and the supernatant isdiscarded.

The cells in the resulting precipitated fraction were thoroughlyloosened, 0.2 to 1 ml of a mixed solution of 2 g of polyethyleneglycol-1000 (PEG-1000), 2 ml of MEM medium and 0.7 ml ofdimethylsulfoxide (DMSO) per 10⁸ antibody-producing cells is added tothe cells under stirring at 37° C., and then 1 to 2 ml of MEM medium isfurther added thereto several times at 1 to 2 minute intervals.

After the addition, MEM medium is added to give a total amount of 50 ml.The resulting prepared solution is centrifuged at 900 rpm for 5 minutes,and then the supernatant is discarded. The cells in the resultingprecipitated fraction were gently loosened and then gently suspended in100 ml of HAT medium (the normal medium to which 10⁻⁴ mol/lhypoxanthine, 1.5×10⁻⁵ mol/l thymidine and 4×10⁻⁷ mol/l aminopterin havebeen added) by repeated drawing up into and discharging from a measuringpipette.

The suspension is poured into a 96 well culture plate at 100 μl/well andcultured at 37° C. for 7 to 14 days in a 5% CO₂ incubator.

After culturing, a part of the culture supernatant is recovered, and ahybridoma which specifically reacts with a partial fragment polypeptideof the polypeptide of the present invention is selected according to theenzyme immunoassay described in Antibodies, A Laboratory manual, ColdSpring Harbor Laboratory, Chapter 14 (1998) and the like.

A specific example of the enzyme immunoassay is described below.

The partial fragment polypeptide of the polypeptide of the presentinvention used as the antigen in the immunization is spread on asuitable plate, is allowed to react with a hybridoma culturingsupernatant or a purified antibody obtained in (d) described below as afirst antibody, and is further allowed to react with an anti-rat oranti-mouse immunoglobulin antibody labeled with an enzyme, a chemicalluminous substance, a radioactive substance or the like as a secondantibody for reaction suitable for the labeled substance. A hybridomawhich specifically reacts with the polypeptide of the present inventionis selected as a hybridoma capable of producing a monoclonal antibody ofthe present invention.

Cloning is repeated using the hybridoma twice by limiting dilutionanalysis (HT medium (a medium in which aminopterin has been removed fromHAT medium) is firstly used, and the normal medium is secondly used),and a hybridoma which is stable and contains a sufficient amount ofantibody titer is selected as a hybridoma capable of producing amonoclonal antibody of the present invention.

(d) Preparation of Monoclonal Antibody

The monoclonal antibody-producing hybridoma cells obtained in (c) areinjected intraperitoneally into 8- to 10-week-old mice or nude micetreated with pristane (intraperitoneal administration of 0.5 ml of2,6,10,14-tetramethylpentadecane (pristane) followed by 2 weeks offeeding) at 5×10⁶ to 20×10⁶ cells/animal. The hybridoma causes ascitestumor in 10 to 21 days.

The ascitic fluid is collected from the mice or nude mice, andcentrifuged to remove solid contents at 3000 rpm for 5 minutes.

A monoclonal antibody can be purified and isolated from the resultingsupernatant according to the method similar to that used in thepolyclonal antibody.

The subclass of the antibody can be determined using a mouse monoclonalantibody typing kit or a rat monoclonal antibody typing kit. Thepolypeptide amount can be determined by the Lowry method or bycalculation based on the absorbance at 280 nm.

The antibody obtained in the above is within the scope of the antibodyof the present invention.

The antibody can be used for the general assay using an antibody, suchas a radioactive material labeled immunoassay (RIA), competitive bindingassay, an immunotissue chemical staining method (ABC method, CSA method,etc.), immunoprecipitation, Western blotting, ELISA assay, and the like(An introduction to Radioimmunoassay and Related Techniques, ElsevierScience (1986); Techniques in Immunocytochemistry, Academic Press, Vol.1 (1982), Vol. 2 (1983) & Vol. 3 (1985); Practice and Theory of EnzymeImmunoassays, Elsevier Science (1985); Enzyme-linked Immunosorbent Assay(ELISA), Igaku Shoin (1976); Antibodies—A Laboratory Manual, Cold SpringHarbor laboratory (1988); Monoclonal Antibody Experiment Manual,Kodansha Scientific (1987); Second Series Biochemical Experiment Course,Vol. 5, Immunobiochemistry Research Method, Tokyo Kagaku Dojin (1986)).

The antibody of the present invention can be used as it is or afterbeing labeled with a label.

Examples of the label include radioisotope, an affinity label (e.g.,biotin, avidin, or the like), an enzyme label (e.g., horseradishperoxidase, alkaline phosphatase, or the like), a fluorescence label(e.g., FITC, rhodamine, or the like), a label using a rhodamine atom,(J. Histochem. Cytochem., 18: 315 (1970); Meth. Enzym., 62: 308 (1979);Immunol., 109: 129 (1972); J. Immunol., Meth., 13: 215 (1979)), and thelike.

Expression of the polypeptide of the present invention, fluctuation ofthe expression, the presence or absence of structural change of thepolypeptide, and the presence or absence in an organism other thancoryneform bacteria of a polypeptide corresponding to the polypeptidecan be analyzed using the antibody or the labeled antibody by the aboveassay, or a polypeptide array or proteome analysis described below.

Furthermore, the polypeptide recognized by the antibody can be purifiedby immunoaffinity chromatography using the antibody of the presentinvention.

12. Production and Use of Polypeptide Array

(1) Production of Polypeptide Array

A polypeptide array can be produced using the polypeptide of the presentinvention obtained in the above item 10 or the antibody of the presentinvention obtained in the above item 11.

The polypeptide array of the present invention includes protein chips,and comprises a solid support and the polypeptide or antibody of thepresent invention adhered to the surface of the solid support.

Examples of the solid support include plastic such as polycarbonate orthe like; an acrylic resin, such as polyacrylamide or the like; complexcarbohydrates, such as agarose, sepharose, or the like; silica; asilica-based material, carbon, a metal, inorganic glass, latex beads,and the like.

The polypeptides or antibodies according to the present invention can beadhered to the surface of the solid support according to the methoddescribed in Biotechniques, 27: 1258-61 (1999); Molecular MedicineToday, 5: 326-7 (1999); Handbook of Experimental Immunology, 4thedition, Blackwell Scientific Publications, Chapter 10 (1986); Meth.Enzym., 34 (1974); Advances in Experimental Medicine and Biology, 42(1974); U.S. Pat. No. 4,681,870; U.S. Pat. No. 4,282,287; U.S. Pat. No.4,762,881, or the like.

The analysis described herein can be efficiently performed by adheringthe polypeptide or antibody of the present invention to the solidsupport at a high density, though a high fixation density is not alwaysnecessary.

(2) Use of Polypeptide Array

A polypeptide or a compound capable of binding to and interacting withthe polypeptides of the present invention adhered to the array can beidentified using the polypeptide array to which the polypeptides of thepresent invention have been adhered thereto as described in the above(1).

Specifically, a polypeptide or a compound capable of binding to andinteracting with the polypeptides of the present invention can beidentified by subjecting the polypeptides of the present invention tothe following steps (i) to (iv):

-   (i) preparing a polypeptide array having the polypeptide of the    present invention adhered thereto by the method of the above (1);-   (ii) incubating the polypeptide immobilized on the polypeptide array    together with at least one of a second polypeptide or compound;-   (iii) detecting any complex formed between the at least one of a    second polypeptide or compound and the polypeptide immobilized on    the array using, for example, a label bound to the at least one of a    second polypeptide or compound, or a secondary label which    specifically binds to the complex or to a component of the complex    after unbound material has been removed; and-   (iv) analyzing the detection data.

Specific examples of the polypeptide array to which the polypeptide ofthe present invention has been adhered include a polypeptide arraycontaining a solid support to which at least one of a polypeptidecontaining an amino acid sequence selected from SEQ ID NOS:3502 to 7001,a polypeptide containing an amino acid sequence in which at least oneamino acids is deleted, replaced, inserted or added in the amino acidsequence of the polypeptide and having substantially the same activityas that of the polypeptide, a polypeptide containing an amino acidsequence having a homology of 60% or more with the amino acid sequencesof the polypeptide and having substantially the same activity as that ofthe polypeptides, a partial fragment polypeptide, and a peptidecomprising an amino acid sequence of a part of a polypeptide.

The amount of production of a polypeptide derived from coryneformbacteria can be analyzed using a polypeptide array to which the antibodyof the present invention has been adhered in the above (1).

Specifically, the expression amount of a gene derived from a mutant ofcoryneform bacteria can be analyzed by subjecting the gene to thefollowing steps (i) to (iv):

-   (i) preparing a polypeptide array by the method of the above (1);-   (ii) incubating the polypeptide array (the first antibody) together    with a polypeptide derived from a mutant of coryneform bacteria;-   (iii) detecting the polypeptide bound to the polypeptide immobilized    on the array using a labeled second antibody of the present    invention; and-   (iv) analyzing the detection data.

Specific examples of the polypeptide array to which the antibody of thepresent invention is adhered include a polypeptide array comprising asolid support to which at least one of an antibody which recognizes apolypeptide comprising an amino acid sequence selected from SEQ IDNOS:3502 to 7001, a polypeptide comprising an amino acid sequence inwhich at least one amino acids is deleted, replaced, inserted or addedin the amino acid sequence of the polypeptide and having substantiallythe same activity as that of the polypeptide, a polypeptide comprisingan amino acid sequence having a homology of 60% or more with the aminoacid sequences of the polypeptide and having substantially the sameactivity as that of the polypeptides, a partial fragment polypeptide, ora peptide comprising an amino acid sequence of a part of a polypeptide.

A fluctuation in an expression amount of a specific polypeptide can bemonitored using a polypeptide obtained in the time course of culture asthe polypeptide derived from coryneform bacteria. The culturingconditions can be optimized by analyzing the fluctuation.

When a polypeptide derived from a mutant of coryneform bacteria is used,a mutated polypeptide can be detected.

13. Identification of Useful Mutation in Mutant by Proteome Analysis

Usually, the proteome is used herein to refer to a method wherein apolypeptide is separated by two-dimensional electrophoresis and theseparated polypeptide is digested with an enzyme, followed byidentification of the polypeptide using a mass spectrometer (MS) andsearching a data base.

The two dimensional electrophoresis means an electrophoretic methodwhich is performed by combining two electrophoretic procedures havingdifferent principles. For example, polypeptides are separated dependingon molecular weight in the primary electrophoresis. Next, the gel isrotated by 90° or 180° and the secondary electrophoresis is carried outdepending on isoelectric point. Thus, various separation patterns can beachieved (JIS K 3600 2474).

In searching the data base, the amino acid sequence information of thepolypeptides of the present invention and the recording medium of thepresent invention provide for in the above items 2 and 8 can be used.

The proteome analysis of a coryneform bacterium and its mutant makes itpossible to identify a polypeptide showing a fluctuation therebetween.

The proteome analysis of a wild type strain of coryneform bacteria and aproduction strain showing an improved productivity of a target productmakes it possible to efficiently identify a mutation protein which isuseful in breeding for improving the productivity of a target product ora protein of which expression amount is fluctuated.

Specifically, a wild type strain of coryneform bacteria and alysine-producing strain thereof are each subjected to the proteomeanalysis. Then, a spot increased in the lysine-producing strain,compared with the wild type strain, is found and a data base is searchedso that a polypeptide showing an increase in yield in accordance with anincrease in the lysine productivity can be identified. For example, as aresult of the proteome analysis on a wild type strain and alysine-producing strain, the productivity of the catalase having theamino acid sequence represented by SEQ ID NO:3785 is increased in thelysine-producing mutant.

As a result that a protein having a high expression level is identifiedby proteome analysis using the nucleotide sequence information and theamino acid sequence information, of the genome of the coryneformbacteria of the present invention, and a recording medium storing thesequences, the nucleotide sequence of the gene encoding this protein andthe nucleotide sequence in the upstream thereof can be searched at thesame time, and thus, a nucleotide sequence having a high expressionpromoter can be efficiently selected.

In the proteome analysis, a spot on the two-dimentional electrophoresisgel showing a fluctuation is sometimes derived from a modified protein.However, the modified protein can be efficiently identified using therecording medium storing the nucleotide sequence information, the aminoacid sequence information, of the genome of coryneform bacteria, and therecording medium storing the sequences, according to the presentinvention.

Moreover, a useful mutation point in a useful mutant can be easilyspecified by searching a nucleotide sequence (nucleotide sequence ofpromoters, ORF, or the like) relating to the thus identified proteinusing a recording medium storing the nucleotide sequence information andthe amino acid sequence information, of the genome of coryneformbacteria of the present invention, and a recording medium storing thesequences and using a primer designed on the basis of the detectednucleotide sequence. As a result that the useful mutation point isspecified, an industrially useful mutant having the useful mutation orother useful mutation derived therefrom can be easily bred.

The present invention will be explained in detail below based onExamples. However, the present invention is not limited thereto.

EXAMPLE 1

Determination of the Full Nucleotide Sequence of Genome ofCorynebacterium glutamicum

The full nucleotide sequence of the genome of Corynebacterium glutamicumwas determined based on the whole genome shotgun method (Science, 269:496-512 (1995)). In this method, a genome library was prepared and theterminal sequences were determined at random. Subsequently, thesesequences were ligated on a computer to cover the full genome.Specifically, the following procedure was carried out.

(1) Preparation of Genome DNA of Corynebacterium glutamicum ATCC 13032

Corynebacterium glutamicum ATCC 13032 was cultured in BY medium (7 g/lmeat extract, 10 g/l peptone, 3 g/l sodium chloride, 5 g/l yeastextract, pH 7.2) containing 1% of glycine at 30° C. overnight and thecells were collected by centrifugation. After washing with STE buffer(10.3% sucrose, 25 mmol/l Tris hydrochloride, 25 mmol/l EDTA, pH 8.0),the cells were suspended in 10 ml of STE buffer containing 10 mg/mllysozyme, followed by gently shaking at 37° C. for 1 hour. Then, 2 ml of10% SDS was added thereto to lyse the cells, and the resultant mixturewas maintained at 65° C. for 10 minutes and then cooled to roomtemperature. Then, 10 ml of Tris-neutralized phenol was added thereto,followed by gently shaking at room temperature for 30 minutes andcentrifugation (15,000×g, 20 minutes, 20° C.). The aqueous layer wasseparated and subjected to extraction with phenol/chloroform andextraction with chloroform (twice) in the same manner. To the aqueouslayer, 3 mol/l sodium acetate solution (pH 5.2) and isopropanol wereadded at 1/10 times volume and twice volume, respectively, followed bygently stirring to precipitate the genome DNA. The genome DNA wasdissolved again in 3 ml of TE buffer (10 mmol/l Tris hydrochloride, 1mmol/l EDTA, pH 8.0) containing 0.02 mg/ml of RNase and maintained at37° C. for 45 minutes. The extractions with phenol, phenol/chloroformand chloroform were carried out successively in the same manner as theabove. The genome DNA was subjected to isopropanol precipitation. Thethus formed genome DNA precipitate was washed with 70% ethanol threetimes, followed by air-drying, and dissolved in 1.25 ml of TE buffer togive a genome DNA solution (concentration: 0.1 mg/ml).

(2) Construction of a Shotgun Library

TE buffer was added to 0.01 mg of the thus prepared genome DNA ofCorynebacterium glutamicum ATCC 13032 to give a total volume of 0.4 ml,and the mixture was treated with a sonicator (Yamato Powersonic Model150) at an output of 20 continuously for 5 seconds to obtain fragmentsof 1 to 10 kb. The genome fragments were blunt-ended using a DNAblunting kit (manufactured by Takara Shuzo) and then fractionated by 6%polyacrylamide gel electrophoresis. Genome fragments of 1 to 2 kb werecut out from the gel, and 0.3 ml MG elution buffer (0.5 mol/l ammoniumacetate, 10 mmol/l magnesium acetate, 1 mmol/l EDTA, 0.1% SDS) was addedthereto, followed by shaking at 37° C. overnight to elute DNA. The DNAeluate was treated with phenol/chloroform, and then precipitated withethanol to obtain a genome library insert. The total insert and 500 ngof pUC18 SmaI/BAP (manufactured by Amersham Pharmacia Biotech) wereligated at 16° C. for 40 hours.

The ligation product was precipitated with ethanol and dissolved in 0.01ml of TE buffer. The ligation solution (0.001 ml) was introduced into0.04 ml of E. coli ELECTRO MAX DH10B (manufactured by Life Technologies)by the electroporation under conditions according to the manufacture'sinstructions. The mixture was spread on LB plate medium (LB medium (10g/l bactotrypton, 5 g/l yeast extract, 10 g/l sodium chloride, pH 7.0)containing 1.6% of agar) containing 0.1 mg/ml ampicillin, 0.1 mg/mlX-gal and 1 mmol/l isopropyl-β-D-thiogalactopyranoside (IPTG) andcultured at 37° C. overnight.

The transformant obtained from colonies formed on the plate medium wasstationarily cultured in a 96-well titer plate having 0.05 ml of LBmedium containing 0.1 mg/ml ampicillin at 37° C. overnight. Then, 0.05ml of LB medium containing 20% glycerol was added thereto, followed bystirring to obtain a glycerol stock.

(3) Construction of Cosmid Library

About 0.1 mg of the genome DNA of Corynebacterium glutamicum ATCC 13032was partially digested with Sau3AI (manufactured by Takara Shuzo) andthen ultracentrifuged (26,000 rpm, 18 hours, 20° C.) under 10 to 40%sucrose density gradient obtained using 10% and 40% sucrose buffers (1mol/l NaCl, 20 mmol/l Tris hydrochloride, 5 mmol/l EDTA, 10% or 40%sucrose, pH 8.0). After the centrifugation, the solution thus separatedwas fractionated into tubes at 1 ml in each tube. After confirming theDNA fragment length of each fraction by agarose gel electrophoresis, afraction containing a large amount of DNA fragment of about 40 kb wasprecipitated with ethanol.

The DNA fragment was ligated to the BamHI site of superCos1(manufactured by Stratagene) in accordance with the manufacture'sinstructions. The ligation product was incorporated into Escherichiacoli XL-1-BlueMR strain (manufactured by Stratagene) using Gigapack IIIGold Packaging Extract (manufactured by Stratagene) in accordance withthe manufacture's instructions. The Escherichia coli was spread on LBplate medium containing 0.1 mg/ml ampicillin and cultured therein at 37°C. overnight to isolate colonies. The resulting colonies werestationarily cultured at 37° C. overnight in a 96-well titer platecontaining 0.05 ml of the LB medium containing 0.1 mg/ml ampicillin ineach well. LB medium containing 20% glycerol (0.05 ml) was addedthereto, followed by stirring to obtain a glycerol stock.

(4) Determination of Nucleotide Sequence

(4-1) Preparation of Template

The full nucleotide sequence of Corynebacterium glutamicum ATCC 13032was determined mainly based on the whole genome shotgun method. Thetemplate used in the whole genome shotgun method was prepared by thePCR-method using the library prepared in the above (2).

Specifically, the clone derived from the whole genome shotgun librarywas inoculated using a replicator (manufactured by GENETIX) into eachwell of a 96-well plate containing the LB medium containing 0.1 mg/ml ofampicillin at 0.08 ml per each well and then stationarily cultured at37° C. overnight.

Next, the culturing solution was transported using a copy plate(manufactured by Tokken) into a 96-well reaction plate (manufactured byPE Biosystems) containing a PCR reaction solution (TaKaRa Ex Taq(manufactured by Takara Shuzo)) at 0.08 ml per each well. Then, PCR wascarried out in accordance with the protocol by Makino et. al. (DNAResearch, 5: 1-9 (1998)) using GeneAmp PCR System 9700 (manufactured byPE Biosystems) to amplify the inserted fragment.

The excessive primers and nucleotides were eliminated using a kit forpurifying a PCR production (manufactured by Amersham Pharmacia Biotech)and the residue was used as the template in the sequencing reaction.

Some nucleotide sequences were determined using a double-stranded DNAplasmid as a template.

The double-stranded DNA plasmid as the template was obtained by thefollowing method.

The clone derived from the whole genome shotgun library was inoculatedinto a 24- or 96-well plate containing a 2× YT medium (16 g/lbactotrypton, 10 g/l yeast extract, 5 g/l sodium chloride, pH 7.0)containing 0.05 mg/ml ampicillin at 1.5 ml per each well and thencultured under shaking at 37° C. overnight.

The double-stranded DNA plasmid was prepared from the culturing solutionusing an automatic plasmid preparing machine, KURABO PI-50 (manufacturedby Kurabo Industries) or a multiscreen (manufactured by Millipore) inaccordance with the protocol provided by the manufacturer.

To purify the double-stranded DNA plasmid using the multiscreen, Biomek2000 (manufactured by Beckman Coulter) or the like was employed.

The thus obtained double-stranded DNA plasmid was dissolved in water togive a concentration of about 0.1 mg/ml and used as the template insequencing.

(4-2) Sequencing Reaction

To 6 μl of a solution of ABI PRISM BigDye Terminator Cycle SequencingReady Reaction Kit (manufactured by PE Biosystems), an M13 regulardirection primer (M13-21) or an M13 reverse direction primer (M13REV)(DNA Research, 5: 1-9 (1998) and the template prepared in the above(4-1) (the PCR product or the plasmid) were added to give 10 μl of asequencing reaction solution. The primers and the templates were used inan amount of 1.6 pmol and an amount of 50 to 200 ng, respectively.

Dye terminator sequencing reaction of 45 cycles was carried out withGeneAmp PCR System 9700 (manufactured by PE Biosystems) using thereaction solution. The cycle parameter was determined in accordance withthe manufacturer's instruction accompanying ABI PRISM BigDye TerminatorCycle Sequencing Ready Reaction Kit. The sample was purified usingMultiScreen HV plate (manufactured by Millipore) according to themanufacture's instructions. The thus purified reaction product wasprecipitated with ethanol, followed by drying, and then stored in thedark at −30° C.

The dry reaction product was analyzed by ABI PRISM 377 DNA Sequencer andABI PRISM 3700 DNA Analyzer (both manufactured by PE Biosystems) each inaccordance with the manufacture's instructions.

The data of about 50,000 sequences in total (i.e., about 42,000sequences obtained using 377 DNA Sequencer and about 8,000 reactionsobtained by 3700 DNA Analyser) were transferred to a server (AlphaServer 4100: manufactured by COMPAQ) and stored. The data of these about50,000 sequences corresponded to 6 times as much as the genome size.

(5) Assembly

All operations were carried out on the basis of UNIX platform. Theanalytical data were output in Macintosh platform using X Window System.The base call was carried out using phred (The University ofWashington). The vector sequence data was deleted using SPS Cross_Match(manufactured by Southwest Parallel Software). The assembly was carriedout using SPS phrap (manufactured by Southwest Parallel Software; ahigh-speed version of phrap (The University of Washington)). The contigobtained by the assembly was analyzed using a graphical editor, consed(The University of Washington). A series of the operations from the basecall to the assembly were carried out simultaneously using a scriptphredPhrap attached to consed.

(6) Determination of Nucleotide Sequence in Gap Part

Each cosmid in the cosmid library constructed in the above (3) wasprepared by a method similar to the preparation of the double-strandedDNA plasmid described in the above (4-1). The nucleotide sequence at theend of the inserted fragment of the cosmid was determined by using ABIPRISM BigDye Terminator Cycle Sequencing Ready Reaction Kit(manufactured by PE Biosystems) according to the manufacture'sinstructions.

About 800 cosmid clones were sequenced at both ends to search anucleotide sequence in the contig derived from the shotgun sequencingobtained in the above (5) coincident with the sequence. Thus, thelinkage between respective cosmid clones and respective contigs weredetermined and mutual alignment was carried out. Furthermore, theresults were compared with the physical map of Corynebacteriumglutamicum ATCC 13032 (Mol. Gen. Genet., 252: 255-265 (1996) to carryingout mapping between the cosmids and the contigs.

The sequence in the region which was not covered with the contigs wasdetermined by the following method.

Clones containing sequences positioned at the ends of contigs wereselected. Among these clones, about 1,000 clones wherein only one end ofthe inserted fragment had been determined were selected and the sequenceat the opposite end of the inserted fragment was determined. A shotgunlibrary clone or a cosmid clone containing the sequences at therespective ends of the inserted fragment in two contigs was identified,the full nucleotide sequence of the inserted fragment of this clone wasdetermined, and thus the nucleotide sequence of the gap part wasdetermined. When no shotgun library clone or cosmid clone covering thegap part was available, primers complementary to the end sequences atthe two contigs were prepared and the DNA fragment in the gap part wasamplified by PCR. Then, sequencing was performed by the primer walkingmethod using the amplified DNA fragment as a template or by the shotgunmethod in which the sequence of a shotgun clone prepared from theamplified DNA fragment was determined. Thus, the nucleotide sequence ofthe domain was determined.

In a region showing a low sequence precision, primers were synthesizedusing AUTOFINISH function and NAVIGATING function of consed (TheUniversity of Washington) and the sequence was determined by the primerwalking method to improve the sequence precision. The thus determinedfull nucleotide sequence of the genome of Corynebacterium glutamicumATCC 13032 strain is shown in SEQ ID NO:1.

(7) Identification of ORF and Presumption of its Function

ORFs in the nucleotide sequence represented by SEQ ID NO:1 wereidentified according to the following method. First, the ORF regionswere determined using software for identifying ORF, i.e., Glimmer,GeneMark and GeneMark.hmm on UNIX platform according to the respectivemanual attached to the software.

Based on the data thus obtained, ORFs in the nucleotide sequencerepresented by SEQ ID NO:1 were identified.

The putative function of an ORF was determined by searching the homologyof the identified amino acid sequence of the ORF against an amino aciddatabase consisting of protein-encoding domains derived from Swiss-Prot,PIR or Genpept database constituted by protein encoding domains derivedfrom GenBank database, Frame Search (manufactured by Compugen), or bysearching the homology of the identified amino acid sequence of the ORFagainst an amino acid database consisting of protein-encoding domainsderived from Swiss-Prot, PIR or Genpept database constituted by proteinencoding domains derived from GenBank database, BLAST. The nucleotidesequences of the thus determined ORFs are shown in SEQ ID NOS:2 to 3501,and the amino acid sequences encoded by these ORFs are shown in SEQ IDNOS:3502 to 7001.

In some cases of the sequence listings in the present invention,nucleotide sequences, such as TTG, TGT, GGT, and the like, other thanATG, are read as an initiating codon encoding Met.

Also, the preferred nucleotide sequences are SEQ ID NOS:2 to 355 and 357to 3501, and the preferred amino acid sequences are shown in SEQ IDNOS:3502 to 3855 and 3957 to 7001

Table 1 shows the registration numbers in the above-described databasesof sequences which were judged as having the highest homology with thenucleotide sequences of the ORFs as the results of the homology searchin the amino acid sequences using the homology-searching software FrameSearch (manufactured by Compugen), names of the genes of thesesequences, the functions of the genes, and the matched length,identities and analogies compared with publicly known amino acidtranslation sequences. Moreover, the corresponding positions wereconfirmed via the alignment of the nucleotide sequence of an arbitraryORF with the nucleotide sequence of SEQ ID NO:1. Also, the positions ofnucleotide sequences other than the ORFs (for example, ribosomal RNAgenes, transfer RNA genes, IS sequences, and the like) on, the genomewere determined.

FIG. 1 shows the positions of typical genes of the Corynebacteriumglutamicum ATCC 13032 on the genome.

TABLE 1 Terminal Identity Similarity Matched length SEQ NO. (DNA) SEQNO. (a.a.) Initial (nt) (nt) ORF (bp) db Match Homologous gene (%) (%)(a.a.) Function 2 3502 1 1572 1572 gsp: R98523 Brevibacterium flavumdnaA 99.8 99.8 524 replication initiation protein DnaA 3 3503 1920 1597324 4 3504 2292 3473 1182 sp: DP3B_MYCSM Mycobacterium smegmatis dnaN50.5 81.8 390 DNA polymerase III beta chain 5 3505 3585 4766 1182 sp:RECF_MYCSM Mycobacterium smegmatis recF 53.3 79.9 392 DNA replicationprotein (recF protein) 6 3506 4766 5299 534 sp: YREG_STRCO Streptomycescoelicolor yreG 35.1 58.1 174 hypothetical protein 7 3507 5354 7486 2133pir: S44198 Mycobacterium tuberculosis 71.9 88.9 704 DNA topoisomerase(ATP- H37Rv gyrB hydrolyzing) 8 3508 7830 8795 966 9 3509 9466 8798 66910 3510 9562 10071 510 11 3511 9914 9474 441 12 3512 11177 10107 1071sp: YV11_MYCTU Mycobacterium tuberculosis 29.4 50.7 422 NAGC/XYLRrepressor H37Rv 13 3513 11523 11263 261 14 3514 11768 11523 246 15 351511831 14398 2568 sp: GYRA_MYCTU Mycobacterium tuberculosis 70.4 88.1 854DNA gyrase subunit A H37Rv Rv0006 gyrA 16 3516 14405 14746 342 pir:E70698 Mycobacterium tuberculosis 29.5 69.6 112 hypothetical membraneprotein H37Rv Rv0007 17 3517 16243 15209 1035 sp: YEIH_ECOLI Escherichiacoli K12 yeiH 33.7 63.5 329 hypothetical protein 18 3518 16314 17207 894gp: AB042619_1 Hydrogenophilus thermoluteolus 27.6 62.3 268 bacterialregulatory protein, LysR TH-1 cbbR type 19 3519 17251 17670 420 20 352018729 17860 870 gp: AF156103_2 Rhodobacter capsulatus ccdA 29.1 57.4 265cytochrome c biogenesis protein 21 3521 19497 18736 762 pir: A49232Coxiella burnetii com1 31.6 64.5 155 hypothetical protein 22 3522 1970520073 369 pir: F70664 Mycobacterium tuberculosis 36.8 70.1 117 repressorH37Rv Rv1846c 23 3523 20073 21065 993 gp: MLCB1788_6 Mycobacteriumleprae 24.9 50.8 321 hypothetical membrane protein MLCB1788.18 24 352421253 21074 180 pir: I40838 Corynebacterium sp. ATCC 65.4 88.5 262,5-diketo-D-gluconic acid reductase 31090 25 3525 21597 22124 528 sp:5NTD_VIBPA Vibrio parahaemolyticus nutA 27.0 56.1 196 5′-nucleotidaseprecursor 26 3526 22164 23399 1236 gp: AE001909_7 Deinococcusradiodurans 27.0 56.7 270 5′-nucleotidase family protein DR0505 27 352723779 23615 165 prf: 2513302C Corynebacterium striatum ORF1 52.9 72.6 51transposase 28 3528 24295 24729 435 prf: 2413353A Xanthomonas campestris51.8 79.9 139 organic hydroperoxide detoxication phaseoli ohr enzyme 293529 26297 24885 1413 sp: RECG_THIFE Thiobacillus ferrooxidans recG 32.760.8 217 ATP-dependent DNA helicase 30 3530 26338 26775 438 31 353128099 26822 1278 sp: AMYH_YEAST Saccharomyces cerevisiae 26.7 54.1 449glucan 1,4-alpha-glucosidase S288C YIR019C sta1 32 3532 29117 28164 954gp: ERU52850_1 Erysipelothrix rhusiopathiae 28.9 63.7 311 lipoproteinewlA 33 3533 29965 29117 849 gp: AF180520_3 Streptococcus pyogenes SF37034.6 74.1 266 ABC 3 transport family or integral mtsC membrane protein34 3534 29995 30651 657 sp: FECE_ECOLI Escherichia coli K12 fecE 39.270.3 222 iron(III) dicitrate transport ATP- biding protein 35 3535 3069731677 981 pir: A72417 Thermotoga maritima MSB8 25.8 56.5 283 sugar ABCtransporter, periplasmic TM0114 sugar-binding protein 36 3536 3167732699 1023 prf: 1207243B Escherichia coli K12 rbsC 30.5 68.3 312 highaffinity ribose transport protein 37 3537 32699 33457 759 sp: RBSA_BACSUBacillus subtilis 168 rbsA 32.2 76.7 236 ribose transport ATP-bindingprotein 38 3538 34280 33465 816 pir: I51116 Petromyzon marinus 23.6 44.4347 neurofilament subunit NF-180 39 3539 34339 34899 561 sp: CYPA_MYCTUMycobacterium leprae H37RV 79.9 89.9 169 peptidyl-prolyl cls-transIsomerase A RV0009 ppiA 40 3540 34982 35668 687 sp: YQGP_BACSU Bacillussubtilis 168 yqgP 29.2 53.1 226 hypothetical membrane protein 41 354137221 38198 978 sp: FEPG_ECOLI Escherichia coli K12 fepG 40.4 70.5 332ferric enterobactin transport system permease protein 42 3542 3724236247 996 43 3543 38202 38978 777 gp: VCU52150_9 Vibrio cholerae viuC51.8 81.8 253 ATPase 44 3544 38978 39799 822 sp: VIUB_VIBVU Vibriovulnificus MO6-24 viuB 26.2 52.7 260 vulnibactin utilization protein 453545 40458 40189 270 sp: YO11_MYCTU Mycobacterium tuberculosis 40.0 72.695 hypothetical membrane protein H37Rv Rv0011c 46 3546 42513 40576 1938sp: PKNB_MYCLE Mycobacterium leprae pknB 40.6 68.7 648 serine/threonineprotein kinase 47 3547 43919 42513 1407 gp: AF094711_1 Streptomycescoelicolor pksC 31.7 59.1 486 serine/threonine protein kinase 48 354845347 43926 1422 gp: AF241575_1 Streptomyces griseus pbpA 33.5 66.7 492penicillin-binding protein 49 3549 46489 45347 1143 sp: SP5E_BACSUBacillus subtilis 168 spoVE 31.2 65.6 375 stage V sporulation protein E50 3550 48021 46669 1353 pir: H70699 Mycobacterium tuberculosis 44.170.8 469 phosphoprotein phosphatase H37Rv ppp 51 3551 48485 48024 462pir: A70700 Mycobacterium tuberculosis 38.7 66.5 155 hypotheticalprotein H37Rv Rv0019c 52 3552 49368 48505 864 pir: B70700 Mycobacteriumtuberculosis 23.6 38.8 526 hypothetical protein H37Rv Rv0020c 53 355349601 49455 147 54 3554 50616 49897 720 55 3555 50972 50754 219 56 355651436 50966 471 57 3557 53055 54008 954 sp: PH2M_TRICU Trichosporoncutaneum ATCC 29.9 63.3 117 phenol 2-monooxygenase 46490 58 3558 5309551626 1470 sp: GABD_ECOLI Escherichia coli K12 gabD 46.7 78.2 490succinate-semialdehyde dehydrogenase (NAD(P)+) 59 3559 54080 55546 1467sp: YRKH_BACSU Bacillus subtilis yrkH 27.3 57.0 242 hypothetical protein60 3560 56417 55629 789 sp: Y441_METJA Methanococcus jannaschii 29.064.1 262 hypothetical membrane protein MJ0441 61 3561 56676 56386 291sp: YRKF_BACSU Bacillus subtilis yrkF 40.5 74.3 74 hypothetical protein62 3562 57270 56680 591 sp: YC61_SYNY3 Synechocystis sp. PCC6803 36.370.4 179 hypothetical protein slr1261 63 3563 57478 57651 174 pir:G70988 Mycobacterium tuberculosis 53.2 83.9 62 hypothetical proteinH37Rv Rv1766 64 3564 58087 58941 855 65 3565 59091 59930 840 gp:LMFL4768_11 Leishmania major L4768.11 26.8 50.7 310 hypothetical protein66 3566 59952 60662 711 67 3567 60669 62321 1653 68 3568 63508 623901119 pir: F70952 Mycobacterium tuberculosis 29.5 59.5 390 magnesium andcobalt transport H37Rv Rv1239c corA protein 69 3569 64040 63594 447 703570 64190 65458 1269 gp: AF179611_12 Zymomonas mobilis ZM4 clcb 30.064.8 400 chloride channel protein 71 3571 66197 65508 690 sp: PNUC_SALTYSalmonella typhimurium pnuC 24.1 53.1 241 required for NMN transport 723572 66851 67972 1122 sp: PHOL_MYCTU Mycobacterium tuberculosis 29.160.0 340 phosphate starvation-induced H37Rv RV2368C protein-like protein73 3573 68170 68301 132 74 3574 68634 68251 384 75 3575 69060 69824 76576 3576 70186 68720 1467 sp: CITM_BACSU Bacillus subtilis citM 42.3 68.8497 Mg(2+)/citrate complex secondary transporter 77 3577 70506 721581653 sp: DPIB_ECOLI Escherichia coli K12 dpiB 27.2 60.6 563two-component system sensor histidine kinase 78 3578 72043 71474 570 793579 72161 72814 654 sp: DPIA_ECOLI Escherichia coli K12 criR 33.2 63.3229 transcriptional regulator 80 3580 73728 72817 912 gp: AF134895_1Corynebacterium glutamicum 43.3 73.7 293 D-isomer specific 2-hydroxyacidunkdh dehydrogenase 81 3581 73844 74272 429 gp: SCM2_3 Streptomycescoelicolor A3(2) 38.6 76.4 127 hypothetical protein SCM2.03 82 358274490 75491 1002 sp: BIOB_CORGL Corynebacterium glutamicum 99.4 99.7 334biotin synthase bioB 83 3583 75506 75742 237 pir: H70542 Mycobacteriumtuberculosis 72.1 79.1 43 hypothetical protein H37Rv Rv1590 84 358475697 76035 339 sp: YKI4_YEAST Saccharomyces cerevisiae 34.1 63.5 85hypothetical protein YKL084w 85 3585 76353 76469 117 86 3586 80753 80613141 PIR: F81737 Chlamydia muridarum Nigg 71.0 75.0 42 hypotheticalprotein TC0129 87 3587 81274 81002 273 GSP: Y35814 Chlamydia pneumoniae61.0 66.0 84 hypothetical protein 88 3588 83568 82120 1449 prf: 2512333AStreptomyces virginiae varS 25.6 59.0 507 Integral membrane effluxprotein 89 3589 84935 83691 1245 gp: D38505_1 Bacillus sp. 97.2 99.8 394creatinine deaminase 90 3590 85403 85098 306 91 3591 86277 85663 615 923592 86318 87241 924 sp: HST2_YEAST Saccharomyces cerevisiae hst2 26.250.2 279 SIR2 gene family (silent information regulator) 93 3593 8853287561 972 prf: 2316378A Propionibacterium acnes 30.7 59.0 251triacylglycerol lipase 94 3594 89444 88545 900 prf: 2316378APropionibacterium acnes 29.4 56.1 262 triacylglycerol lipase 95 359589558 90445 888 96 3596 90973 90461 513 gp: AB029154_1 Corynebacteriumglutamicum 90.6 94.7 171 transcriptional regulator ureR 97 3597 9117491473 300 gp: AB029154_2 Corynebacterium glutamicum 100.0 100.0 100urease gammma subunit or urease ureA structural protein 98 3598 9150391988 486 gp: CGL251883_2 Corynebacterium glutamicum 100.0 100.0 162urease beta subunit ATCC 13032 ureB 99 3599 91992 93701 1710 gp:CGL251883_3 Corynebacterium glutamicum 100.0 100.0 570 urease alphasubunit ATCC 13032 ureC 100 3600 93729 94199 471 gp: CGL251883_4Corynebacterium glutamicum 100.0 100.0 157 urease accessory protein ATCC13032 ureE 101 3601 94202 94879 678 gp: CGL251883_5 Corynebacteriumglutamicum 100.0 100.0 226 urease accessory protein ATCC 13032 ureF 1023602 94899 95513 615 gp: CGL251883_6 Corynebacterium glutamicum 100.0100.0 205 urease accessory protein ATCC 13032 ureG 103 3603 95517 96365849 gp: CGL251883_7 Corynebacterium glutamicum 100.0 100.0 283 ureaseaccessory protein ATCC 13032 ureD 104 3604 97144 96368 777 prf: 2318326BAgrobacterium radiobacter echA 21.2 48.4 279 epoxide hydrolase 105 360597521 98189 669 106 3606 98470 97319 1152 gp: AF148322_1 Streptomycesviridifaciens vlmF 26.5 59.7 347 valanimycin resistant protein 107 360799819 100493 675 108 3608 101582 98808 2775 109 3609 103435 101612 1824sp: HTPG_ECOLI Escherichia coli K12 htpG 23.8 52.7 668 heat shockprotein (hsp90-family) 110 3610 103494 104909 1416 sp: AMN_ECOLIEscherichia coli K12 amn 41.0 68.2 481 AMP nucleosidase 111 3611 105751105173 579 112 3612 106392 105841 552 pir: E72483 Aeropyrum pernix K1APE2509 29.6 58.7 196 acetolactate synthase large subunit 113 3613107289 106630 660 114 3614 107435 110890 3456 sp: PUTA_SALTY Salmonellatyphimurium putA 25.8 50.4 1297 proline dehydrogenase/P5C dehydrogenase115 3615 111161 111274 114 116 3616 111374 112318 945 sp: AAD_PHACHPhanerochaete chrysosporium 30.2 60.7 338 aryl-alcohol dehydrogenase aad(NADP+) 117 3617 112470 114083 1614 sp: YDAH_ECOLI Escherichia coli K12ydaH 36.5 71.4 513 pump protein (transport) 118 3618 114147 115478 1332prf: 2422424A Enterobacter agglomerans 23.0 49.2 352 Indole-3-acetyl-Asphydrolase 119 3619 115262 114564 699 120 3620 115578 115943 366 sp:YIDH_ECOLI Escherichia coli K12 yidH 35.9 70.8 106 hypothetical membraneprotein 121 3621 115949 116263 315 122 3622 118599 116548 2052 123 3623119589 118810 780 sp: ACCR_AGRTU Agrobacterium tumefaciens 29.5 59.7 258transcriptional repressor accR 124 3624 120021 120410 390 pir: C70019Bacillus subtilis yurT 57.9 78.6 126 methylglyoxalase 125 3625 120922120413 510 sp: YC76_MYCTU Mycobacterium tuberculosis 37.0 64.8 162hypothetical protein H37Rv Rv1276c 126 3626 122459 120951 1509 prf:2309180A Pseudomonas fluorescens mtlD 43.5 70.4 497 mannitoldehydrogenase 127 3627 123841 122507 1335 prf: 2321326A Klebsiellapneumoniae dalT 30.3 68.3 435 D-arabinitol transporter 128 3628 123842124030 189 129 3629 124130 124966 837 sp: GATR_ECOLI Escherichia coliK12 gatR 27.3 64.6 260 galactitol utilization operon repressor 130 3630124932 126350 1419 sp: XYLB_STRRU Streptomyces rubiginosus xylB 45.068.1 451 xylulose kinase 131 3631 127171 127992 822 132 3632 127189126353 837 gp: CGPAN_2 Corynebacterium glutamicum 100.0 100.0 279pantoate-beta-alanine ligase ATCC 13032 panC 133 3633 128004 127192 813gp: CGPAN_1 Corynebacterium glutamicum 100.0 100.0 2713-methyl-2-oxobutanoate ATCC 13032 panB hydroxymethyltransferase 1343634 129049 128099 951 135 3635 130118 129489 630 sp: 3MG_ARATHArabidopsis thaliana mag 42.0 67.6 188 DNA-3-methyladenine glycosylase136 3636 130145 130798 654 137 3637 131738 130815 924 gp: AB029896_1Petroleum-degrading bacterium 39.3 69.3 270 esterase HD-1 hde 138 3638131798 132424 627 139 3639 132424 132981 558 sp: CAH_METTEMethanosarcina thermophila 30.9 53.2 201 carbonate dehydratase 140 3640134113 132971 1143 sp: XYLR_BACSU Bacillus subtilis W23 xylR 24.1 49.3357 xylose operon repressor protein 141 3641 135478 134207 1272 gp:LLLPK214_12 Lactococcus lactis mef214 21.1 61.2 418 macrolide effluxprotein 142 3642 136321 135518 804 143 3643 136565 136122 444 144 3644136804 138744 1941 145 3645 138791 140329 1539 146 3646 139861 139226636 147 3647 140329 141789 1461 pir: I39714 Agrobacterium tumefacienscelA 24.3 51.2 420 cellulose synthase 148 3648 141796 143526 1731 sp:HKR1_YEAST Saccharomyces cerevisiae 25.1 51.8 593 hypothetical membraneprotein YDR420W hkr1 149 3649 142455 143075 621 150 3650 143575 1446391065 151 3651 144725 145480 756 152 3652 146396 145518 879 sp:RARD_PSEAE Pseudomonas aeruginosa rarD 34.7 60.7 303 chloramphenicolsensitive protein 153 3653 146522 147238 717 sp: YADS_ECOLI Escherichiacoli K12 yadS 30.3 59.1 198 hypothetical membrane protein 154 3654147238 147570 333 155 3655 148122 149780 1659 156 3656 150930 1497941137 sp: ABRB_ECOLI Escherichia coli K12 abrB 32.4 62.3 361 transportprotein 157 3657 151572 152369 798 sp: YFCA_ECOLI Escherichia coli K12yfcA 34.7 70.2 248 hypothetical membrane protein 158 3658 151589 150966624 159 3659 152410 152814 405 160 3660 155613 153226 2388 sp:HRPB_ECOLI Escherichia coli K12 hrpB 33.8 64.3 829 ATP-dependenthelicase 161 3661 155853 156167 315 162 3662 156821 156147 675 sp:NODL_RHILV Rhizobium leguminosarum bv. 40.4 66.0 188 nodulation proteinviciae plasmid pRL1JI nodL 163 3663 156848 157537 690 sp: ALKB_ECOLIEscherichia coli o373#1 alkB 34.7 60.7 219 DNA repair system specificfor alkylated DNA 164 3664 157614 158138 525 sp: 3MG1_ECOLI Escherichiacoli K12 tag 39.8 65.1 166 DNA-3-methyladenine glycosylase 165 3665158154 158831 678 sp: RHTC_ECOLI Escherichia coli K12 rhtC 34.1 61.3 217threonine efflux protein 166 3666 158869 159159 291 sp: YAAA_BACSUBacillus subtilis yaaA 50.9 72.7 55 hypothetical protein 167 3667 159162160013 852 prf: 2510326B Streptomyces peucetius dnrV 31.0 52.1 284doxorubicin biosynthesis enzyme 168 3668 160029 160370 342 gp:SPAC1250_3 Schizosaccharomyces pombe 35.6 56.7 104 methyltransferaseSPAC1250.04c 169 3669 160431 161360 930 170 3670 161696 162352 657 1713671 162295 161363 933 172 3672 162463 162867 405 gp: AE002420_13Neisseria meningitidis MC58 41.5 76.3 118 ribonuclease NMB0662 173 3673162965 163603 639 174 3674 165717 166457 741 175 3675 165755 163689 2067gp: AF176569_1 Mus musculus nl1 28.5 57.2 722 neprilysin-likemetallopeptidase 1 176 3676 166457 167419 963 177 3677 168595 167837 759sp: FARR_ECOLI Escherichia coli K12 farR 29.8 65.6 238 transcriptionalregulator, GntR family or fatty acyl-responsive regulator 178 3678168975 169991 1017 pir: T14544 Beta vulgaris 28.6 63.0 332 fructokinaseor carbohydrate kinase 179 3679 169996 170916 921 gp: SC8F11_3Streptomyces coelicolor A3(2) 52.7 80.7 296 hypothetical proteinSC8F11.03c 180 3680 170933 172444 1512 prf: 2204281A Streptomycescoelicolor msdA 61.0 86.1 498 methylmalonic acid semialdehydedehydrogenase 181 3681 172468 173355 888 sp: IOLB_BACSU Bacillussubtilis iolB 33.2 58.2 268 myo-inositol catabolism 182 3682 173548175275 1728 sp: IOLD_BACSU Bacillus subtilis iolD 41.0 69.8 586myo-inositol catabolism 183 3683 175319 176272 954 sp: MOCC_RHIMERhizobium meliloti mocC 29.7 51.0 290 rhizopine catabolism protein 1843684 176308 177318 1011 sp: MI2D_BACSU Bacillus subtilis idh or iolG39.1 72.2 335 myo-inositol 2-dehydrogenase 185 3685 177334 178203 870sp: IOLH_BACSU Bacillus subtilis iolH 44.6 72.1 287 myo-inositolcatabolism 186 3686 178285 179658 1374 sp: TCMA_STRGA Streptomycesglaucescens tcmA 30.9 61.5 457 metabolite export pump of tetracenomycinC resistance 187 3687 179081 178461 621 188 3688 179689 180711 1023 sp:YVAA_BACSU Bacillus subtilis yvaA 31.1 65.5 354 oxidoreductase 189 3689180842 181297 456 190 3690 181264 181647 384 191 3691 182679 181687 993gp: SRE9798_1 Streptomyces reticuli cebR 32.0 61.9 331 regulatoryprotein 192 3692 182819 184051 1233 sp: Y4HM_RHISN Rhizobium sp. NGR234y4hM 24.4 52.5 442 oxidoreductase 193 3693 184077 185087 1011 sp:YFIH_BACSU Bacillus subtilis yfiH 33.7 64.7 303 hypothetical protein 1943694 185214 185642 429 195 3695 186508 186708 201 sp: CSP_ARTGOStreptomyces coelicolor A3(2) 70.3 92.2 64 cold shock protein csp 1963696 186769 187302 534 197 3697 187302 187607 306 198 3698 187687 188100414 prf: 2113413A Stellaria longipes 30.6 58.2 134 caffeoyl-CoA3-O-methyltransferase 199 3699 188725 188300 426 200 3700 189736 188747990 sp: CCPA_BACSU Bacillus subtilis ccpA 28.7 62.1 338glucose-resistance amylase regulator regulator 201 3701 189920 190321402 202 3702 190628 190389 240 203 3703 192175 190703 1473 sp:XYLT_LACBR Lactobacillus brevis xylT 36.0 70.5 458 D-xylose protonsymporter 204 3704 193248 192949 300 205 3705 193262 194464 1203 gp:AF189147_1 Corynebacterium glutamicum 100.0 100.0 401 transposase(ISCg2) ATCC 13032 tnp 206 3706 195038 194604 435 sp: FIXL_RHIMERhizobium meliloti fixL 27.6 60.7 145 signal-transducing histidinekinase 207 3707 195240 199769 4530 gp: AB024708_1 Corynebacteriumglutamicum 99.9 100.0 1510 glutamine 2-oxoglutarate gltBaminotransferase large subunit 208 3708 199772 201289 1518 gp:AB024708_2 Corynebacterium glutamicum 99.4 99.8 506 glutamine2-oxoglutarate gltD aminotransferase small subunit 209 3709 201580201341 240 210 3710 203244 201760 1485 pir: C70793 Mycobacteriumtuberculosis 44.6 72.8 496 hypothetical protein H37Rv Rv3698 211 3711205588 205956 369 212 3712 206068 206385 318 213 3713 207011 203541 3471prf: 2224383C Mycobacterium avium embB 39.8 70.6 1122 arabinosyltransferase 214 3714 208989 207007 1983 pir: D70697 Mycobacteriumtuberculosis 35.0 66.1 651 hypothetical membrane protein H37Rv Rv3792215 3715 209968 209210 759 prf: 2504279B Pseudomonas sp. phbB 31.4 56.5223 acetoacetyl CoA reductase 216 3716 211455 209992 1464 pir: B70697Mycobacterium tuberculosis 66.0 85.1 464 oxidoreductase H37Rv Rv3790 2173717 211768 211535 234 218 3718 211777 212283 507 219 3719 212283 212735453 220 3720 212656 213657 1002 gp: LMA243459_1 Leishmania major ppg124.3 57.4 350 proteophosphoglycan 221 3721 213712 214107 396 sp:Y0GN_MYCTU Mycobacterium tuberculosis 60.5 83.9 124 hypothetical proteinH37Rv Rv3789 222 3722 214121 214522 402 223 3723 214527 215159 633 pir:H70666 Mycobacterium tuberculosis 43.2 73.8 206 hypothetical proteinH37Rv Rv1864c 224 3724 216100 215162 939 pir: B70696 Mycobacteriumtuberculosis 63.6 79.1 302 rhamnosyl transferase H37Rv Rv3782 rfbE 2253725 216264 216605 342 226 3726 216712 216116 597 gp: AB016260_100Agrobacterium tumefaciens 31.3 55.1 214 hypothetical protein plasmidpTi-SAKURA tiorf100 227 3727 217929 217141 789 sp: RFBE_YEREN Yersiniaenterocolitica rfbE 47.0 78.4 236 O-antigen export system ATP- bindingprotein 228 3728 218746 217943 804 sp: RFBD_YEREN Yersiniaenterocolitica rfbD 31.3 75.6 262 O-antigen export system permeaseprotein 229 3729 218979 220151 1173 pir: F70695 Mycobacteriumtuberculosis 36.5 63.0 416 hypothetical protein H37Rv Rv3778c 230 3730221107 220154 954 gp: AF010309_1 Homo sapiens pig3 41.1 71.5 302 NADPHquinone oxidoreductase 231 3731 221712 221131 582 232 3732 221911 222207297 PIR: A70606 Mycobacterium tuberculosis 35.0 51.0 78 probableelectron transfer protein H37Rv Rv3571 233 3733 223685 222210 1476 sp:ALST_BACSU Bacillus subtilis alsT 46.7 75.8 475 amino acid carrierprotein 234 3734 224336 225244 909 235 3735 226324 225242 1083 gp:SYPCCMOEB_1 Synechococcus sp. PCC 7942 43.8 70.1 368 molybdopterinbiosynthesis protein moeB moeB (sulfurylase) 236 3736 226767 226312 456prf: 2403296D Arthrobacter nicotinovorans 44.7 75.3 150 molybdopterinsynthase, large moaE subunit 237 3737 227230 226760 471 sp: MOCB_SYNP7Synechococcus sp. PCC 7942 33.5 63.3 158 molybdenum cofactorbiosynthesis moaCB protein CB 238 3738 227685 227218 468 prf: 2403296CArthrobacter nicotinovorans 61.7 84.4 154 co-factor synthesis proteinmoaC 239 3739 228887 227703 1185 gp: ANY10817_2 Arthrobacternicotinovorans 34.5 58.6 377 molybdopterin co-factor synthesis moeAprotein 240 3740 229613 228891 723 prf: 2403296F Arthrobacternicotinovorans 44.1 70.5 227 hypothetical membrane protein modB 241 3741230514 229711 804 prf: 2403296E Arthrobacter nicotinovorans 34.0 68.0256 molybdate-binding periplasmic modA protein 242 3742 230608 230928321 pir: D70816 Mycobacterium tuberculosis 37.5 70.8 96 molybdopterinconverting factor H37Rv moaD2 subunit 1 243 3743 231842 230931 912 prf:2518354A Thermococcus litoralis malK 34.3 60.8 365 maltose transportprotein 244 3744 232267 231848 420 sp: YPT3_STRCO Streptomycescoelicolor A3(2) 36.4 76.9 121 hypothetical membrane protein ORF3 2453745 233282 232260 1023 sp: HIS8_ZYMMO Zymomonas mobilis hisC 37.3 65.8330 histidinol-phosphate aminotransferase 246 3746 233913 234818 906 2473747 235203 234910 294 248 3748 235290 235409 120 249 3749 236212 235451762 gp: BAU81286_1 Brucella abortus oxyR 29.4 57.1 252 transcriptionfactor 250 3750 236326 237342 1017 sp: ADH2_BACST Bacilliusstearothermophilus 34.0 66.0 335 alcohol dehydrogenase DSM 2334 adh 2513751 237345 238145 801 sp: PUO_MICRU Micrococcus rubens puo 21.5 38.1451 putrescine oxidase 252 3752 238176 239525 1350 prf: 2305239ABorrelia burgdorferi mgtE 30.9 68.5 444 magnesium ion transporter 2533753 239772 239945 174 254 3754 239986 241515 1530 prf: 2320140A Xenopuslaevis 33.2 59.6 567 Na/dicarboxylate cotransporter 255 3755 242902241883 1020 pir: C70800 Mycobacterium tuberculosis 46.1 69.1 317oxidoreductase H37Rv tyrA 256 3756 242910 243431 522 pir: B70800Mycobacterium tuberculosis 48.8 73.8 160 hypothetical protein H37RvRv3753c 257 3757 243494 243910 417 gp: RHBNFXP_1 Bradyrhizobiumjaponicum 45.1 70.1 144 nitrogen fixation protein 258 3758 244015 244215201 259 3759 244466 244816 351 260 3760 244902 247304 2403 sp:YV34_MYCTU Mycobacterium tuberculosis 20.7 45.7 997 membrane transportprotein H37Rv Rv0507 mmpL2 261 3761 247310 248572 1263 sp: TGT_ZYMMOZymomonas mobilis 41.3 68.0 400 queuine tRNA-ribosyltransferase 262 3762249294 248557 738 sp: YPDP_BACSU Bacillus subtilis ypdP 28.1 62.1 203hypothetical membrane protein 263 3763 249428 250507 1080 264 3764250369 249722 648 265 3765 250503 251939 1437 pir: S65588 Streptomycesglaucescens strW 24.3 49.6 526 ABC transporter 266 3766 251952 252830879 sp: SYE_BACSU Bacillus subtilis gltX 34.8 63.3 316 glutamyl-tRNAsynthetase 267 3767 253819 252830 990 268 3768 255438 254329 1110 gp:PSESTBCBAD_1 Pseudomonas syringae tnpA 34.2 55.0 360 transposase 2693769 255794 255492 303 270 3770 256067 256204 138 271 3771 256599 2578941296 gsp: W69554 Brevibacterium lactofermentum 98.6 100.0 432 aspartatetransaminase aspC 272 3772 257900 258529 630 273 3773 258551 260875 2325gp: AF025391_1 Thermus thermophilus dnaX 31.6 53.1 642 DNA polymeraseIII holoenzyme tau subunit 274 3774 259312 258596 717 275 3775 260987261295 309 sp: YAAK_BACSU Bacillus subtilis yaaK 41.6 74.3 101hypothetical protein 276 3776 261402 262055 654 sp: RECR_BACSU Bacillussubtilis recR 42.5 72.4 214 recombination protein 277 3777 263295 262546750 prf: 2503462B Heliobacillus mobilis cobQ 38.3 61.7 248 cobyric acidsynthase 278 3778 264566 263298 1269 prf: 2503462C Heliobacillus mobilismurC 31.3 60.6 444 UDP-N-acetylmuramyl tripeptide synthetase 279 3779265678 264599 1080 pir: H70794 Mycobacterium tuberculosis 25.7 55.2 346DNA polymerase III epsilon chain H37Rv dnaQ 280 3780 269124 268258 867sp: YLEU_CORGL Corynebacterium glutamicum 100.0 100.0 270 hypotheticalmembrane protein (Brevibacterium flavum) ATCC 13032 orfX 281 3781 269371270633 1263 sp: AKAB_CORGL Corynebacterium glutamicum 99.5 99.8 421aspartate kinase alpha chain lysC-alpha 282 3782 270576 269524 1053 2833783 271761 273194 1434 284 3784 274120 273542 579 prf: 2312309AMycobacterium smegmatis sigE 31.2 63.5 189 extracytoplasmic functionalternative sigma factor 285 3785 274366 275871 1506 sp: CATV_BACSUBacillus subtilis katA 52.9 76.4 492 vegetative catalase 286 3786 275891276232 342 287 3787 276247 275957 291 288 3788 276763 276302 462 sp:LRP_KLEPN Klebsiella pneumoniae lrp 37.1 72.0 143 leucine-responsiveregulatory protein 289 3789 276829 277581 753 sp: AZLC_BACSU Bacillussubtilis 1A1 aziC 30.5 68.0 203 branched-chain amino acid transport 2903790 277581 277904 324 291 3791 278301 277987 315 292 3792 278732 278388345 gp: AF178758_1 Sinorhizobium sp. As4 arsR 34.4 68.9 90metalloregulatory protein 293 3793 278814 279893 1080 gp: AF178758_2Sinorhizobium sp. As4 arsB 52.2 84.2 341 arsenic oxyanion-translocationpump membrane subunit 294 3794 279893 280279 387 sp: ARSC_STAXYStaphylococcus xylosus arsC 31.1 68.9 119 arsenate reductase 295 3795280666 280349 318 296 3796 280939 280670 270 297 3797 281401 280949 453298 3798 282933 281404 1530 gp: AF097740_4 Bacillus firmus OF4 mrpD 32.470.4 503 Na+/H+ antiporter or multiple resistance and pH regulationrelated protein D 299 3799 283317 282937 381 prf: 2504285DStaphylococcus aureus mnhC 37.0 70.6 119 Na+/H+ antiporter 300 3800286202 283317 2886 gp: AF097740_1 Bacillus firmus OF4 mrpA 34.1 64.3 824Na+/H+ antiporter or multiple resistance and pH regulation relatedprotein A 301 3801 286373 287857 1485 302 3802 287661 287059 603 3033803 288829 287966 864 304 3804 289796 289131 666 sp: CZCR_ALCEUAlcaligenes eutrophus CH34 38.6 70.4 223 transcriptional activator czcR305 3805 291243 289777 1467 prf: 2214304B Mycobacterium tuberculosis26.7 56.8 521 two-component system sensor mtrB histidine kinase 306 3806291815 292417 603 sp: APL_LACLA Lactococcus lactis MG1363 apl 28.3 60.0180 alkaline phosphatase 307 3807 291833 291273 561 308 3808 293511292597 915 pir: B69865 Bacillus subtilis ykuE 26.1 54.7 307phosphoesterase 309 3809 293539 293991 453 sp: YQEY_BACSU Bacillussubtilis yqeY 37.6 71.8 149 hypothetical protein 310 3810 296388 2940042385 prf: 2209359A Mycobacterium leprae pon1 48.3 77.1 782 class Apenicillin-binding protein(PBP1) 311 3811 297064 297402 339 pir: S20912Streptomyces coelicolor A3(2) 40.9 63.4 71 regulatory protein whiB 3123812 297431 297622 192 313 3813 297631 297783 153 gp: SCH17_10Streptomyces coelicolor A3(2) 84.0 96.0 50 hypothetical proteinSCH17.10c 314 3814 297792 298250 459 pir: G70790 Mycobacteriumtuberculosis 65.1 89.9 149 transcriptional regulator H37Rv Rv3678c 3153815 299684 298332 1353 sp: SHIA_ECOLI Escherichia coli K12 shiA 37.368.9 440 shikimate transport protein 316 3816 300087 300695 609 317 3817301261 299726 1536 sp: LCFA_BACSU Bacillus subtilis lcfA 31.1 59.9 534long-chain-fatty-acid—CoA ligase 318 3818 302036 301512 525 gp: SCJ4_28Streptomyces coelicolor A3(2) 33.9 65.4 127 transcriptional regulatorSCJ4.28c 319 3819 302167 303099 933 sp: FABG_BACSU Bacillus subtilisfabG 41.0 72.5 251 3-oxoacyl-(acyl-carrier-protein) reductase 320 3820303133 304074 942 sp: FLUG_EMENI Emericella nidulans fluG 27.2 52.0 254glutamine synthetase 321 3821 304070 305263 1194 prf: 2512386AArabidopsis thaliana atg6 38.8 66.5 394 short-chain acyl CoA oxidase 3223822 305288 305758 471 sp: NODN_RHILV Rhizobium leguminosarum nodN 45.872.6 153 nodulation protein 323 3823 305858 306700 843 pir: F70790Mycobacterium tuberculosis 41.2 72.4 272 hydrolase H37Rv Rv3677c 3243824 306367 305195 1173 325 3825 306800 307504 705 326 3826 307462306782 681 prf: 2323349A Vibrio cholerae crp 30.9 65.7 207 cAMP receptorprotein 327 3827 307918 307727 192 328 3828 307955 308734 780 sp:UVEN_MICLU Micrococcus luteus pdg 57.5 77.1 240 ultravioletN-glycosylase/AP lyase 329 3829 308745 309302 558 pir: B70790Mycobacterium tuberculosis 34.6 58.3 211 cytochrome c biogenesis proteinH37Rv Rv3673c 330 3830 309370 310038 669 sp: YEAB_ECOLI Escherichia coliK12 yeaB 30.7 56.3 192 hypothetical protein 331 3831 310135 311325 1191pir: H70789 Mycobacterium tuberculosis 38.6 71.0 396 serine proteinaseH37Rv Rv3671c 332 3832 312891 311899 993 prf: 2411250A Corynebacteriumsp. C12 cEH 29.6 52.1 280 epoxide hydrolase 333 3833 313457 312909 549pir: F70789 Mycobacterium tuberculosis 46.8 77.6 156 hypotheticalmembrane protein H37Rv Rv3669 334 3834 314590 313625 966 pir: S72914Mycobacterium leprae 29.6 65.5 287 phosphoserine phosphataseMTCY20G9.32C. serB 335 3835 314980 316002 1023 pir: E70788 Mycobacteriumtuberculosis 35.0 60.2 349 hypothetical protein H37Rv Rv3660c 336 3836316110 317132 1023 pir: C44020 Escherichia coli trbB 32.9 66.5 319conjugal transfer region protein 337 3837 316964 316350 615 338 3838317078 317893 816 pir: C70788 Mycobacterium tuberculosis 30.5 63.7 262hypothetical membrane protein H37Rv Rv3658c 339 3839 317920 318465 546pir: B70788 Mycobacterium tuberculosis 33.8 64.2 201 hypotheticalprotein H37Rv Rv3657c 340 3840 318492 318689 198 pir: A70788Mycobacterium tuberculosis 47.5 84.8 59 hypothetical protein H37RvRv3656c 341 3841 318696 319013 318 342 3842 318958 318545 414 343 3843318991 319335 345 344 3844 321690 319336 2355 sp: YPRA_BACSU Bacillussubtilis yprA 33.8 66.1 764 ATP-dependent RNA helicase 345 3845 322007322207 201 sp: CSP_ARTGO Arthrobacter globiformis SI55 68.7 88.1 67 coldshock protein csp 346 3846 322216 321992 225 347 3847 322910 325897 2988pir: G70563 Mycobacterium tuberculosis 61.7 81.6 977 DNA topoisomerase IH37Rv Rv3646c topA 348 3848 325904 326614 711 349 3849 327735 3266951041 sp: CYAB_STIAU Stigmatella aurantiaca B17R20 32.7 62.4 263adenylate cyclase cyaB 350 3850 328283 329539 1257 sp: DP3X_BACSUBacillus subtilis dnaX 25.3 52.7 423 DNA polymerase III subunittau/gamma 351 3851 329748 329909 162 352 3852 329933 330376 444 gp:AE002103_3 Ureaplasma urealyticum uu033 32.6 59.0 144 hypotheticalprotein 353 3853 330973 331533 561 gp: AE001882_8 Deinococcusradiodurans 39.0 63.4 172 hypothetical protein DR0202 354 3854 331552332433 882 sp: RLUC_ECOLI Escherichia coli K12 rluC 43.6 65.0 314ribosomal large subunit pseudouridine synthase C 355 3855 332919 3345621644 sp: BGLX_ERWCH Erwinia chrysanthemi D1 bgxA 34.8 60.2 558beta-glucosidase/xylosidase 356 3856 332965 334953 1989 gp: AF090429_2Azospirillum irakense salB 38.6 61.4 101 beta-glucosidase 357 3857335009 336112 1104 sp: FADH_AMYME Amycolatopsis methanolica 66.6 86.5362 NAD/mycothiol-dependent formaldehyde dehydrogenase 358 3858 335805335185 621 359 3859 336212 336748 537 sp: YTH5_RHOSN Rhodococcuserythropolis orf5 32.5 47.5 160 metallo-beta-lactamase superfamily 3603860 336781 337449 669 sp: FABG_ECOLI Escherichia coli K12 fabG 25.955.8 251 3-oxoacyl-(acyl-carrier-protein) reductase 361 3861 337539338768 1230 gp: AF148322_1 Streptomyces viridifaciens vlmF 26.3 56.4 415valanimycin resistant protein 362 3862 338793 339725 933 prf: 2512357BActinoplanes sp. acbB 33.8 66.3 320 dTDP-glucose 4,6-dehydratase 3633863 340569 340195 375 pir: A70562 Mycobacterium tuberculosis 59.3 88.9108 hypothetical protein H37Rv Rv3632 364 3864 341327 340569 759 sp:YC22_METJA Methanococcus jannaschii JAL- 33.9 66.5 230 dolicholphosphate mannose 1 MJ1222 synthase 365 3865 341347 342375 1029 366 3866342417 343451 1035 sp: YEFJ_ECOLI Escherichia coli K12 yefJ 25.8 57.3260 nucleotide sugar synthetase 367 3867 343636 345717 2082 sp:USHA_SALTY Salmonella typhimurium ushA 26.1 54.4 586 UDP-sugar hydrolase368 3868 345975 345814 162 369 3869 346460 346110 351 370 3870 348019346961 1059 sp: ADH_MYCTU Mycobacterium tuberculosis 52.2 74.9 343NADP-dependent alcohol H37Rv adhC dehydrogenase 371 3871 348952 348098855 sp: RFBA_SALAN Salmonella anatum M32 rfbA 62.8 84.9 285glucose-1-phosphate thymidylyltransferase 372 3872 350310 348952 1359gp: D78182_5 Streptococcus mutans rmlC 49.5 74.0 192dTDP-4-keto-L-rhamnose reductase 373 3873 351443 350313 1131 sp:RMLB_STRMU Streptococcus mutans XC rmlB 61.8 83.4 343 dTDP-glucose4,6-dehydratase 374 3874 351948 351370 579 sp: NOX_THETH Thermusaquaticus HB8 nox 35.4 61.2 206 NADH dehydrogenase 375 3875 352693353637 945 prf: 2510361A Staphylococcus aureus sirA 33.2 66.5 325Fe-regulated protein 376 3876 354387 353749 639 377 3877 355906 3545991308 sp: Y17M_MYCTU Mycobacterium tuberculosis 37.4 68.3 423hypothetical membrane protein H37Rv Rv3630 378 3878 357228 355849 1380gp: SC5F2A_19 Streptomyces coelicolor 34.1 62.5 461 metallopeptidaseSC5F2A.19c 379 3879 359354 357237 2118 prf: 2502226A Sphingomonascapsulata 28.4 56.4 708 prolyl endopeptidase 380 3880 360334 359762 573381 3881 361905 360814 1092 gp: SCF43_2 Streptomyces coelicolor A3(2)26.0 46.0 258 hypothetical membrane protein 382 3882 363151 362057 1095gsp: W56155 Corynebacterium 50.7 76.6 363 cell surface layer proteinammoniagenes ATCC 6872 383 3883 363824 365257 1434 prf: 2404346BAcinetobacter johnsonii ptk 28.5 57.2 453 autophosphorylating proteinTyr kinase 384 3884 365250 365852 603 prf: 2404346A Acinetobacterjohnsonii ptp 39.2 68.6 102 protein phosphatase 385 3885 365855 366838984 386 3886 366832 368643 1812 sp: CAPD_STAAU Staphylococcus aureus McapD 33.0 65.7 613 capsular polysaccharide biosynthesis 387 3887 368642367701 942 PRF: 2109288X Vibrio cholerae 41.0 51.0 90 ORF 3 388 3888368647 369801 1155 prf: 2423410L Campylobacter jejuni wlaK 37.1 68.3 394lipopolysaccharide biosynthesis/ aminotransferase 389 3889 369794 370405612 gp: AF014804_1 Neisseria meningitidis pglB 54.6 75.0 196 pilinglycosylation protein 390 3890 370613 371773 1161 sp: CAPM_STAAUStaphylococcus aureus M capM 33.4 69.2 380 capsular polysaccharidebiosynthesis 391 3891 371929 373419 1491 pir: S67859 Xanthomonascampestris gumJ 34.3 69.8 504 lipopolysaccharide biosynthesis/ exportprotein 392 3892 373500 374813 1314 sp: MURA_ENTCL Enterobacter cloacaemurA 31.4 64.6 427 UDP-N-acetylglucosamine 1- carboxyvinyltransferase393 3893 374833 375837 1005 sp: MURB_BACSU Bacillus subtilis murB 34.868.5 273 UDP-N- acetylenolpyruvoylglucosamine reductase 394 3894 375842376876 1035 gp: VCLPSS_9 Vibrio cholerae ORF39 × 2 32.0 57.3 356 sugartransferase 395 3895 377683 377832 150 prf: 2211295A Corynebacteriumglutamicum 60.4 79.3 53 transposase 396 3896 378093 378227 135 397 3897378185 378511 327 pir: S43613 Corynebacterium glutamicum 75.7 94.3 70transposase (insertion sequence ATCC 31831 IS31831) 398 3898 378562378287 276 399 3899 379837 378668 1170 pir: G70539 Mycobacteriumtuberculosis 28.0 57.4 404 hypothetical protein H37Rv Rv1565c 400 3900380842 379850 993 gsp: W37352 Pseudomonas aeruginosa PAO1 34.5 60.2 354acetyltransferase psbC 401 3901 381265 381495 231 PIR: S60890Corynebacterium glutamicum 44.0 53.0 65 hypothetical protein B 402 3902381948 383108 1161 sp: UDG8_ECOLI Escherichia coli ugd 63.7 89.7 388UDP-glucose 6-dehydrogenase 403 3903 383768 383496 273 404 3904 385190383982 1209 405 3905 386195 385374 822 gp: AF172324_3 Escherichia coliwbnA 32.1 65.0 243 glycosyl transferase 406 3906 386556 387200 645 gp:AB008676_13 Escherichia coli 0157 wbhH 33.0 62.0 221 acetyltransferase407 3907 387657 387463 195 408 3908 387692 389098 1407 gp: CGLPD_1Corynebacterium glutamicum 99.6 100.0 469 dihydrolipoamide dehydrogenaseATCC 13032 lpd 409 3909 389248 390168 921 pir: JC4985 Xanthomonascampestris 41.7 68.1 295 UTP—glucose-1-phosphate uridylyltransferase 4103910 390233 390730 498 gp: PAU49666_2 Pseudomonas aeruginosa PAO1 43.871.9 153 regulatory protein orfX 411 3911 392208 390787 1422 pir: E70828Mycobacterium tuberculosis 57.0 81.3 477 transcriptional regulator H37RvRv0465c 412 3912 392705 393475 771 gp: SCM10_12 Streptomyces coelicolorA3(2) 34.8 67.4 230 cytochrome b subunit SCM10.12c 413 3913 393639395513 1875 pir: A27763 Bacillus subtilis sdhA 32.4 61.2 608 succinatedehydrogenase flavoprotein 414 3914 395426 396262 837 gp: BMSDHCAB_4Paenibacillus macerans sdhB 27.5 56.2 258 succinate dehydrogenasesubunit B 415 3915 396315 396650 336 416 3916 396672 396932 261 417 3917397040 396411 630 418 3918 397730 397825 96 419 3919 397884 398222 339420 3920 398206 397232 975 gp: SCC78_5 Streptomyces coelicolor 26.3 49.8259 hypothetical protein SCC78.05 421 3921 398329 399579 1251 sp:YJIN_ECOLI Escherichia coli K12 yjiN 32.7 64.3 431 hypothetical protein422 3922 399598 400017 420 423 3923 400039 400341 303 424 3924 400473401150 678 sp: TCMR_STRGA Streptomyces glaucescens 26.4 53.8 197tetracenomycin C transcription GLA.0 tcmR repressor 425 3925 401050401253 204 426 3926 401150 402796 1647 gp: AF164961_8 Streptomycesfradiae T#2717 36.1 74.6 499 transporter urdJ 427 3927 402799 4044301632 gp: AF164961_8 Streptomyces fradiae T#2717 39.6 74.6 508transporter urdJ 428 3928 405419 404508 912 sp: PURU_CORSPCorynebacterium sp. P-1 purU 40.9 72.7 286 formyltetrahydrofolatedeformylase 429 3929 405480 406145 666 sp: DEOC_BACSU Bacillus subtilisdeoC 38.5 74.0 208 deoxyribose-phosphate aldolase 430 3930 406310 406161150 431 3931 406417 405521 897 432 3932 406550 407416 867 prf: 2413441KMycobacterium avium GIR10 26.8 53.6 280 hypothetical protein mav346 4333933 407708 407409 300 pir: A70907 Mycobacterium tuberculosis 58.7 85.992 hypothetical protein H37Rv Rv0190 434 3934 408546 409145 600 435 3935409975 407711 2265 sp: CTPB_MYCLE Mycobacterium leprae ctpB 45.7 75.3748 cation-transporting P-type ATPase B 436 3936 410476 410027 450 4373937 410683 412545 1863 sp: AMYH_YEAST Saccharomyces cerevisiae 27.356.1 626 glucan 1,4-alpha-glucosidase S288C YIR019C sta1 438 3938 412557413633 1077 gp: AF109162_1 Corynebacterium diphtheriae 57.2 83.6 348hemin-binding periplasmic protein hmuT 439 3939 413643 414710 1068 gp:AF109162_2 Corynebacterium diphtheriae 65.2 90.3 330 ABC transporterhmuU 440 3940 414714 415526 813 gp: AF109162_3 Corynebacteriumdiphtheriae 63.8 85.0 254 ABC transporter ATP-binding protein hmuV 4413941 415643 416599 957 gp: SCC75A_17 Streptomyces coelicolor C75A 28.656.4 266 hypothetical protein SCC75A.17c 442 3942 416603 417439 837 gp:SCC75A_17 Streptomyces coelicolor C75A 32.6 61.6 258 hypotheticalprotein SCC75A.17c 443 3943 418354 417545 810 444 3944 419253 418441 813445 3945 419757 419257 501 446 3946 419785 420885 1101 gp: ECOMURBA_1Escherichia coli RDD012 murB 30.1 58.4 356UDP-N-acetylpyruvoylglucosamine reductase 447 3947 420866 421516 651 4483948 421043 420309 735 449 3949 421858 422031 174 450 3950 423793 4220901704 sp: LCFA_BACSU Bacillus subtilis lcfA 35.5 68.1 558long-chain-fatty-acid—CoA ligase 451 3951 423878 425131 1254 gp: SC2G5_6Streptomyces coelicolor 33.9 58.7 416 transferase SC2G5.06 452 3952425177 425920 744 sp: PMGY_STRCO Streptomyces coelicolor A3(2) 70.7 84.2246 phosphoglycerate mutase gpm 453 3953 425934 427172 1239 prf:2404434A Mycobacterium bovis senX3 49.2 74.8 417 two-component systemsensor histidine kinase 454 3954 427172 427867 696 prf: 2404434BMycobacterium bovis BCG 75.8 90.9 231 two-component response regulatorregX3 455 3955 428561 429439 879 456 3956 432023 429438 2586 gp:SCE25_30 Streptomyces coelicolor A3(2) 31.3 60.7 921 ABC transporterATP-binding protein SCE25.30 457 3957 433028 432126 903 sp: YV21_MYCTUMycobacterium tuberculosis 45.0 66.9 269 cytochrome P450 H37Rv RV3121458 3958 433062 433988 927 prf: 2512277A Pseudomonas aeruginosa ppx 28.857.8 306 exopolyphosphatase 459 3959 434010 434822 813 sp: YV23_MYCTUMycobacterium tuberculosis 28.8 57.3 302 hypothetical membrane proteinH37Rv Rv0497 460 3960 434886 435695 810 sp: PROC_CORGL Corynebacteriumglutamicum 100.0 100.0 269 pyrroline-5-carboxylate reductase ATCC 17965proC 461 3961 434986 433865 1122 gp: D88733_1 Equine herpesvirus 1 ORF7125.4 52.0 394 membrane glycoprotein 462 3962 435940 436137 198 pir:S72921 Mycobacterium leprae 76.4 94.6 55 hypothetical proteinB2168_C1_172 463 3963 436321 436103 219 464 3964 436463 436561 99 gp:SCE68_25 Streptomyces coelicolor 89.7 100.0 29 hypothetical proteinSCE68.25c 465 3965 436573 436764 192 466 3966 437233 437850 618 467 3967438044 436980 1065 pir: S72914 Mycobacterium leprae 51.0 77.4 296phosphoserine phosphatase MTCY20G9.32C. serB 468 3968 438179 438424 246sp: YV35_MYCTU Mycobacterium tuberculosis 40.5 66.2 74 hypotheticalprotein H37Rv Rv0508 469 3969 438294 438037 258 470 3970 438516 4399041389 sp: HEM1_MYCLE Mycobacterium leprae hemA 44.4 74.3 455glutamyl-tRNA reductase 471 3971 439909 440814 906 pir: S72887Mycobacterium leprae hem3b 50.7 75.3 308 hydroxymethylbilane synthase472 3972 441220 441591 372 473 3973 442482 441601 882 sp: CATM_ACICAAcinetobacter calcoaceticus 27.1 57.6 321 cat operon transcriptionalregulator catM 474 3974 442758 444158 1401 sp: SHIA_ECOLI Escherichiacoli K12 shiA 35.5 72.2 417 shikimate transport protein 475 3975 444185446038 1854 sp: 3SHD_NEUCR Neurospora crassa qa4 28.2 57.9 3093-dehydroshikimate dehydratase 476 3976 446538 447386 849 gp: AF124518_2Corynebacterium glutamicum 98.2 98.6 282 shikimate dehydrogenase ASO19aroE 477 3977 447670 447398 273 478 3978 449179 448130 1050 sp:POTG_ECOLI Escherichia coli K12 potG 34.7 68.6 363 putrescine transportprotein 479 3979 449714 449100 615 480 3980 450826 449183 1644 sp:SFUB_SERMA Serratia marcescens sfuB 25.1 55.2 578 iron(III)-transportsystem permease protein 481 3981 450849 451961 1113 482 3982 451895450837 1059 gp: SHU75349_1 Brachyspira hyodysenteriae bitA 25.1 59.9 347periplasmic-iron-binding protein 483 3983 452661 454430 1770 pir: S72909Mycobacterium leprae cysG 46.5 71.6 486 uroporphyrin-IIIC-methyltransferase 484 3984 454450 454875 426 485 3985 454967 4559831017 sp: HEM2_STRCO Streptomyces coelicolor A3(2) 60.8 83.1 337delta-aminolevulinic acid hemB dehydratase 486 3986 456016 456597 582487 3987 456641 457150 510 488 3988 457357 459900 2544 sp: CTPB_MYCLEMycobacterium leprae ctpB 27.4 56.5 858 cation-transporting P-typeATPase B 489 3989 459425 458583 843 490 3990 460020 461093 1074 sp:DCUP_STRCO Streptomyces coelicolor A3(2) 55.0 76.7 364 uroporphyrinogendecarboxylase hemE 491 3991 461112 462455 1344 sp: PPOX_BACSU Bacillussubtilis hemY 28.0 59.9 464 protoporphyrinogen IX oxidase 492 3992462557 463867 1311 sp: GSA_MYCLE Mycobacterium leprae hemL 61.7 83.5 425glutamate-1-semialdehyde 2,1- aminomutase 493 3993 463867 464472 606 sp:PMG2_ECOLI Escherichia coli K12 gpmB 28.0 62.7 161 phosphoglyceratemutase 494 3994 464482 465102 621 pir: A70545 Mycobacterium tuberculosis44.7 71.2 208 hypothetical protein H37Rv Rv0526 495 3995 465118 465909792 pir: B70545 Mycobacterium tuberculosis 53.5 85.3 245 cytochromec-type biogenesis H37Rv ccsA protein 496 3996 465949 467571 1623 pir:C70545 Mycobacterium tuberculosis 50.7 76.0 533 hypothetical membraneprotein H37Rv Rv0528 497 3997 467648 468658 1011 pir: D70545Mycobacterium tuberculosis 44.1 77.8 338 cytochrome c biogenesis proteinH37Rv ccsB 498 3998 469370 470170 801 499 3999 470184 470654 471 pir:G70790 Mycobacterium tuberculosis 38.9 69.4 144 transcriptionalregulator H37Rv Rv3678c pb5 500 4000 471013 470657 357 prf: 2420312AStaphylococcus aureus zntR 31.1 72.2 90 Zn/Co transport repressor 5014001 471420 471121 300 502 4002 471515 471847 333 pir: F70545Mycobacterium tuberculosis 39.0 78.1 82 hypothetical membrane proteinH37Rv Rv0531 503 4003 472808 471915 894 sp: MENA_ECOLI Escherichia coliK12 menA 33.6 61.5 301 1,4-dihydroxy-2-naphthoate octaprenyltransferase504 4004 472948 473811 864 gp: AF125164_6 Bacteroides fragilis wcgB 32.462.6 238 glycosyl transferase 505 4005 475136 473814 1323 prf: 2423270BRhizobium trifolii matB 25.4 51.5 421 malonyl-CoA-decarboxylase 506 4006475407 474997 411 sp: YQJF_ECOLI Escherichia coli K12 yqjF 35.3 65.5 139hypothetical membrane protein 507 4007 477048 475489 1560 pir: S27612Pseudomonas putida 50.4 76.0 520 ketoglutarate semialdehydedehydrogenase 508 4008 477995 477048 948 sp: KDGD_PSEPU Pseudomonasputida KDGDH 48.5 75.6 303 5-dehydro-4-deoxyglucarate dehydratase 5094009 478970 478092 879 sp: ALSR_BACSU Bacillus subtilis 168 alsR 36.966.2 293 als operon regulatory protein 510 4010 479303 478989 315 pir:B70547 Mycobacterium tuberculosis 33.0 64.9 94 hypothetical proteinH37Rv Rv0543c 511 4011 480154 480597 444 512 4012 480201 479452 750 gp:SSP277295_9 Sphingomonas sp. LB126 fldB 28.1 54.7 2672-pyrone-4,6-dicarboxylic acid 513 4013 480624 480208 417 514 4014481001 480624 378 515 4015 481391 481131 261 516 4016 482668 481394 1275pir: D70547 Mycobacterium tuberculosis 60.0 83.2 410 low-affinityinorganic phosphate H37Rv pitA transporter 517 4017 483587 483366 222518 4018 483942 483637 306 519 4019 485062 484106 957 sp: MENB_BACSUBacillus subtilis menB 48.5 70.3 293 naphthoate synthase 520 4020 485384485986 603 gp: AE001957_12 Deinococcus radiodurans 57.9 82.7 202peptidase E DR1070 521 4021 485385 485077 309 pir: C70304 Aquifexaeolicus VF5 phhB 37.7 68.8 77 pterin-4a-carbinolamine dehydratase 5224022 486001 487014 1014 pir: D70548 Mycobacterium tuberculosis 54.0 76.7335 muconate cycloisomerase H37Rv Rv0553 menC 523 4023 487028 4886561629 sp: MEND_BACSU Bacillus subtilis menD 29.4 54.0 606 2-oxoglutaratedecarboxylase and 2- succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase 524 4024 488660 489100 441 pir:G70548 Mycobacterium tuberculosis 37.2 64.9 148 hypothetical membraneprotein H37Rv Rv0556 525 4025 489209 490447 1239 pir: H70548Mycobacterium tuberculosis 22.8 54.2 408 alpha-D-mannose-alpha(1-6)H37Rv pimB phosphatidyl myo-inositol monomannoside transferase 526 4026490580 491938 1359 sp: CYCA_ECOLI Escherichia coli K12 cycA 66.2 89.9447 D-serine/D-alanine/glycine transporter 527 4027 491966 492655 690sp: UBIE_ECOLI Escherichia coli K12 ubiE 37.1 66.7 237ubiquinone/menaquinone biosynthesis methyltransferase 528 4028 492915493583 669 529 4029 493916 492645 1272 pir: D70549 Mycobacteriumtuberculosis 49.0 76.7 412 oxidoreductase H37Rv Rv0561c 530 4030 494061495110 1050 sp: HEP2_BACST Bacillus stearothermophilus 39.2 67.1 316heptaprenyl diphosphate synthase ATCC 10149 hepT component II 531 4031496810 497142 333 gp: AF130462_2 Corynebacterium glutamicum 100.0 100.0111 preprotein translocase SecE subunit ATCC 13032 secE 532 4032 497374498327 954 gp: AF130462_3 Corynebacterium glutamicum 100.0 100.0 318transcriptional antiterminator protein ATCC 13032 nusG 533 4033 498598499032 435 gp: AF130462_4 Corynebacterium glutamicum 100.0 100.0 145 50Sribosomal protein L11 ATCC 13032 rplK 534 4034 499162 499869 708 gp:AF130462_5 Corynebacterium glutamicum 100.0 100.0 236 50S ribosomalprotein L1 ATCC 13032 rplA 535 4035 501436 499925 1512 gp: SC5H4_2Streptomyces coelicolor 23.1 50.2 564 regulatory protein SC5H4.02 5364036 501577 502920 1344 sp: GABT_MYCTU Mycobacterium tuberculosis 60.582.4 443 4-aminobutyrate aminotransferase H37Rv RV2589 gabT 537 4037502925 504283 1359 sp: GABD_ECOLI Escherichia coli K12 gabD 40.8 71.8461 succinate-semialdehyde dehydrogenase (NAD(P)+) 538 4038 503739503272 468 GP: ABCARRA_2 Azospirillum brasilense carR 32.0 38.0 150novel two-component regulatory system 539 4039 504379 505569 1191 sp:TYRP_ECOLI Escherichia coli K12 o341#7 25.5 49.9 447 tyrosine-specifictransport protein tyrP 540 4040 505698 507647 1950 sp: CTPG_MYCTUMycobacterium tuberculosis 33.2 64.4 615 cation-transporting ATPase GH37Rv RV1992C ctpG 541 4041 507669 509081 1413 sp: P49_STRLIStreptomyces lividans P49 40.2 66.2 468 hypothetical protein ordehydrogenase 542 4042 509094 509696 603 543 4043 509998 510510 513 sp:RL10_STRGR Streptomyces griseus N2-3-11 52.9 84.7 170 50S ribosomalprotein L10 rplJ 544 4044 510591 510974 384 sp: RL7_MYCTU Mycobacteriumtuberculosis 72.3 89.2 130 50S ribosomal protein L7/L12 H37Rv RV0652rplL 545 4045 511126 510989 138 546 4046 511536 512507 972 pir: A70962Mycobacterium tuberculosis 25.8 55.5 283 hypothetical membrane proteinH37Rv Rv0227c 547 4047 512913 516407 3495 sp: RPOB_MYCTU Mycobacteriumtuberculosis 75.4 90.4 1180 DNA-directed RNA polymerase beta H37RvRV0667 rpoB chain 548 4048 516494 520492 3999 sp: RPOC_MYCTUMycobacterium tuberculosis 72.9 88.7 1332 DNA-directed RNA polymerasebeta H37Rv RV0668 rpoC chain 549 4049 519277 518696 582 GP: AF121004_1Mycobacterium tuberculosis 39.0 52.0 169 hypothetical protein H37RvJv0166c 550 4050 520671 520850 180 551 4051 520865 521644 780 gp:SCJ9A_15 Streptomyces coelicolor A3(2) 39.2 63.8 232 DNA-binding proteinSCJ9A.15c 552 4052 522476 521679 798 sp: YT08_MYCTU Mycobacteriumtuberculosis 29.3 57.7 215 hypothetical protein H37Rv RV2908C 553 4053522694 523059 366 sp: RS12_MYCIT Mycobacterium intracellulare 90.9 97.5121 30S ribosomal protein S12 rpsL 554 4054 523069 523533 465 sp:RS7_MYCSM Mycobacterium smegmatis 81.8 94.8 154 30S ribosomal protein S7LR222 rpsG 555 4055 523896 526010 2115 sp: EFG_MICLU Micrococcus luteusfusA 71.7 88.9 709 elongation factor G 556 4056 526070 523911 2160 5574057 526156 526013 144 558 4058 527121 526894 228 GSP: Y37841 Chlamydiatrachomatis 56.0 78.0 44 lipoprotein 559 4059 527759 527607 153 560 4060528040 528768 729 561 4061 529570 528779 792 sp: FEPC_ECOLI Escherichiacoli K12 fepC 56.2 83.7 258 ferric enterobactin transport ATP- bindingprotein 562 4062 530626 529592 1035 sp: FEPG_ECOLI Escherichia coli K12fepG 45.6 77.8 329 ferric enterobactin transport protein 563 4063 531782530748 1035 sp: FEPD_ECOLI Escherichia coli K12 fepD 48.1 80.6 335ferric enterobactin transport protein 564 4064 532008 532523 516 gp:CTACTAGEN_1 Thermoanaerobacterium 56.6 79.3 145 butyryl-CoA: acetatecoenzyme A thermosaccharolyticum actA transferase 565 4065 533099 533401303 sp: RS10_PLARO Planobispora rosea ATCC 84.2 99.0 101 30S ribosomalprotein S10 53733 rpsJ 566 4066 533437 534090 654 sp: RL3_MYCBOMycobacterium bovis BCG rplC 66.5 89.6 212 50S ribosomal protein L3 5674067 534087 533401 687 568 4068 534090 534743 654 sp: RL4_MYCBOMycobacterium bovis BCG rplD 71.2 90.1 212 50S ribosomal protein L4 5694069 534746 535048 303 sp: RL23_MYCBO Mycobacterium bovis BCG rplW 74.090.6 96 50S ribosomal protein L23 570 4070 535072 534746 327 571 4071535076 535915 840 sp: RL2_MYCLE Mycobacterium bovis BCG rplB 80.7 92.9280 50S ribosomal protein L2 572 4072 535935 536210 276 sp: RS19_MYCTUMycobacterium tuberculosis 87.0 98.9 92 30S ribosomal protein S19 H37RvRv0705 rpsS 573 4073 536183 535899 285 574 4074 536217 536576 360 sp:RL22_MYCTU Mycobacterium tuberculosis 74.3 91.7 109 50S ribosomalprotein L22 H37Rv Rv0706 rplV 575 4075 536579 537322 744 sp: RS3_MYCBOMycobacterium bovis BCG rpsC 77.4 91.2 239 30S ribosomal protein S3 5764076 537328 537741 414 sp: RL16_MYCBO Mycobacterium bovis BCG rplP 69.388.3 137 50S ribosomal protein L16 577 4077 537744 537971 228 sp:RL29_MYCBO Mycobacterium bovis BCG rpmC 65.7 88.1 67 50S ribosomalprotein L29 578 4078 537977 538252 276 sp: RS17_MYCBO Mycobacteriumbovis BCG rpsQ 69.5 89.0 82 30S ribosomal protein S17 579 4079 538267537974 294 580 4080 538698 538381 318 581 4081 539413 538718 696 5824082 539741 540106 366 sp: RL14_MYCTU Mycobacterium tuberculosis 83.695.1 122 50S ribosomal protein L14 H37Rv Rv0714 rplN 583 4083 540112540423 312 sp: RL24_MYCTU Mycobacterium tuberculosis 76.2 91.4 105 50Sribosomal protein L24 H37Rv Rv0715 rplX 584 4084 540426 540998 573 sp:RL5_MICLU Micrococcus luteus rplE 73.6 92.3 183 50S ribosomal protein L5585 4085 541048 542079 1032 586 4086 542896 542090 807 sp: 2DKG_CORSPCorynebacterium sp. 52.3 74.2 260 2,5-diketo-D-gluconic acid reductase587 4087 543412 542921 492 588 4088 544329 543415 915 sp: FDHD_WOLSUWolinella succinogenes fdhD 28.9 59.7 298 formate dehydrogenase chain D589 4089 544670 544335 336 gp: SCGD3_29 Streptomyces coelicolor A3(2)37.2 68.1 94 molybdopterin-guanine dinucleotide SCGD3.29c biosynthesisprotein 590 4090 546889 544757 2133 sp: FDHF_ECOLI Escherichia coli fdfF24.3 53.4 756 formate dehydrogenase H or alpha chain 591 4091 547329548084 756 592 4092 548990 548187 804 593 4093 550651 548990 1662 sp:YC81_MYCTU Mycobacterium tuberculosis 26.9 52.6 624 ABC transporterATP-binding protein H37Rv Rv1281c oppD 594 4094 551844 550699 1146 5954095 552927 551854 1074 596 4096 554129 552948 1182 pir: E69424Archaeoglobus fulgidus AF1398 24.7 50.4 405 hypothetical protein 5974097 554919 554452 468 gp: AE001931_13 Deinococcus radiodurans 42.7 66.7150 hypothetical protein DR0763 598 4098 555331 555726 396 pir: S29885Micrococcus luteus 75.8 97.7 132 30S ribosomal protein S8 599 4099555749 556282 534 pir: S29886 Micrococcus luteus 59.2 87.7 179 50Sribosomal protein L6 600 4100 556289 556690 402 sp: RL18_MICLUMicrococcus luteus rplR 67.3 90.9 110 50S ribosomal protein L18 601 4101556734 557366 633 sp: RS5_MICLU Micrococcus luteus rpsE 67.8 88.3 17130S ribosomal protein S5 602 4102 557373 557555 183 sp: RL30_ECOLIEscherichia coli K12 rpmJ 54.6 76.4 55 50S ribosomal protein L30 6034103 557565 558008 444 sp: RL15_MICLU Micrococcus luteus rplO 66.4 87.4143 50S ribosomal protein L15 604 4104 557588 556860 729 605 4105 558517558197 321 prf: 2204281A Streptomyces coelicolor msdA 46.9 68.8 128methylmalonic acid semialdehyde dehydrogenase 606 4106 558969 558607 363607 4107 559805 560260 456 GP: ABCARRA_2 Azospirillum brasilense carR47.0 52.0 125 novel two-component regulatory system 608 4108 560634559144 1491 prf: 2516398E Rhodococcus rhodochrous 41.7 71.5 487 aldehydedehydrogenase or betaine plasmid pRTL1 orf5 aldehyde dehydrogenase 6094109 561368 560634 735 610 4110 562632 562937 306 611 4111 562633 5613681266 prf: 2411257B Sphingomonas sp. redA2 41.1 71.6 409 reductase 6124112 562963 562646 318 prf: 2313248B Rhodobacter capsulatus fdxE 47.766.4 107 2Fe2S ferredoxin 613 4113 563736 562993 744 gp: PPU24215_2Pseudomonas putida cymB 35.8 70.8 257 p-cumic alcohol dehydrogenase 6144114 563871 564083 213 PIR: H72754 Aeropyrum pernix K1 APE0029 50.0 56.050 hypothetical protein 615 4115 565471 563732 1740 pir: JC4176Pyrococcus furiosus Vc1 DSM 22.9 45.0 629 phosphoenolpyruvate synthetase3638 ppsA 616 4116 566759 565680 1080 pir: JC4176 Pyrococcus furiosusVc1 DSM 38.6 66.7 378 phosphoenolpyruvate synthetase 3638 ppsA 617 4117568088 566799 1290 prf: 2104333G Rhodococcus erythropolis thcB 34.8 65.2422 cytochrome P450 618 4118 569075 568272 804 prf: 2512309A Erwiniacarotovora carotovora 28.5 66.0 256 transcriptional repressor kdgR 6194119 570774 571316 543 sp: KAD_MICLU Micrococcus luteus adk 48.9 81.0184 adenylate kinase 620 4120 571367 570756 612 621 4121 571476 572267792 sp: AMPM_BACSU Bacillus subtilis 168 map 43.1 74.7 253 methionineaminopeptidase 622 4122 572349 573176 828 623 4123 573407 573622 216pir: F69644 Bacillus subtilis infA 77.0 86.0 72 translation initiationfactor IF-1 624 4124 573816 574181 366 prf: 2505353B Thermusthermophilus HB8 66.4 91.0 122 30S ribosomal protein S13 rps13 625 4125574187 574588 402 sp: RS11_STRCO Streptomyces coelicolor A3(2) 81.3 93.3134 30S ribosomal protein S11 SC6G4.06. rpsK 626 4126 574615 575217 603prf: 2211287F Mycobacterium tuberculosis 82.6 93.9 132 30S ribosomalprotein S4 H37Rv RV3458C rpsD 627 4127 575338 576351 1014 sp: RPOA_BACSUBacillus subtilis 168 rpoA 51.1 77.8 311 RNA polymerase alpha subunit628 4128 575366 575211 156 629 4129 576410 576898 489 sp: RL17_ECOLIEscherichia coli K12 rplQ 51.6 77.1 122 50S ribosomal protein L17 6304130 577057 577923 867 sp: TRUA_ECOLI Escherichia coli k12 truA 37.061.1 265 pseudouridylate synthase A 631 4131 578033 580429 2397 pir:G70695 Mycobacterium tuberculosis 24.8 51.2 786 hypothetical membraneprotein H37Rv Rv3779 632 4132 580891 580436 456 633 4133 581221 580919303 634 4134 581406 582662 1257 pir: A70836 Mycobacterium tuberculosis27.4 53.8 485 hypothetical protein H37Rv Rv0283 635 4135 582684 5842281545 sp: DIM_ARATH Arabidopsis thaliana CV DIM 22.8 50.9 505 cellelongation protein 636 4136 584268 585620 1353 sp: CFA_ECOLI Escherichiacoli K12 cfa 30.7 56.0 423 cyclopropane-fatty-acyl-phospholipid synthase637 4137 585823 586248 426 gp: SCL2_30 Streptomyces coelicolor A3(2)28.0 59.0 100 hypothetical membrane protein SCL2.30c 638 4138 587757586399 1359 sp: ELYA_BACAO Bacillus alcalophilus 31.3 58.0 273high-alkaline serine proteinase 639 4139 589015 587645 1371 pir: T10930Streptomyces coelicolor A3(2) 24.0 50.6 516 hypothetical membraneprotein SC3C3.21 640 4140 589296 592862 3567 pir: E70977 Mycobacteriumtuberculosis 65.0 38.4 1260 hypothetical membrane protein H37Rv Rv3447c641 4141 590411 589590 822 642 4142 590560 589898 663 643 4143 592862593761 900 644 4144 593935 594258 324 pir: C70977 Mycobacteriumtuberculosis 31.1 69.9 103 hypothetical protein H37Rv Rv3445c 645 4145594293 594580 288 prf: 2111376A Mycobacterium tuberculosis 36.3 81.3 80early secretory antigen target ESAT- 6 protein 646 4146 594939 595379441 sp: RL13_STRCO Streptomyces coelicolor A3(2) 58.6 82.1 145 50Sribosomal protein L13 SC6G4.12. rplM 647 4147 595382 595927 546 sp:RS9_STRCO Streptomyces coelicolor A3(2) 49.2 72.4 181 30S ribosomalprotein S9 SG6G4.13. rpsl 648 4148 596109 597449 1341 prf: 2320260AStaphylococcus aureus 48.9 76.4 450 phosphoglucosamine mutase femR315649 4149 597892 598194 303 650 4150 598194 599702 1509 pir: S75138Synechocystis sp. PCC6803 29.3 45.6 318 hypothetical protein slr1753 6514151 599350 598778 573 652 4152 599699 599932 234 653 4153 600876 600022855 pir: S73000 Mycobacterium leprae 44.0 72.2 259 hypothetical proteinB229_F1_20 654 4154 600971 602053 1083 sp: ALR_MYCTU Mycobacteriumtuberculosis 41.6 68.5 368 alanine racemase H37Rv RV3423C alr 655 4155602080 602574 495 sp: Y097_MYCTU Mycobacterium tuberculosis 48.7 78.6154 hypothetical protein H37Rv Rv3422c 656 4156 602811 604409 1599 sp:YIDE_ECOLI Escherichia coli K12 yidE 28.9 66.2 550 hypothetical membraneprotein 657 4157 604470 605708 1239 gp: PSJ00161_1 Propionibacteriumshermanii pip 51.3 77.6 411 proline iminopeptidase 658 4158 605718606392 675 sp: Y098_MYCTU Mycobacterium tuberculosis 52.2 75.4 207hypothetical protein H37Rv Rv3421c 659 4159 606392 606898 507 sp:RIMI_ECOLI Escherichia coli K12 riml 30.3 59.9 132ribosomal-protein-alanine N- acetyltransferase 660 4160 606905 6079361032 sp: GCP_PASHA Pasteurella haemolytica 46.1 75.2 319O-sialoglycoprotein endopeptidase SEROTYPE A1 gcp 661 4161 607958 6096791722 sp: Y115_MYCTU Mycobacterium tuberculosis 38.4 59.4 571hypothetical protein H37Rv Rv3433c 662 4162 609747 610175 429 663 4163610268 609816 453 664 4164 610348 610644 297 sp: CH10_MYCTUMycobacterium tuberculosis 76.0 94.0 100 heat shock protein groES H37RvRV3418C mopB 665 4165 610659 612272 1614 sp: CH61_MYCLE Mycobacteriumleprae 63.3 85.1 537 heat shock protein groEL B229_C3_248 groE1 666 4166611200 610946 255 GP: MSGTCWPA_1 Mycobacterium tuberculosis 50.0 56.0 76hypothetical protein 667 4167 612266 611109 1158 GP: MSGTCWPA_3Mycobacterium tuberculosis 34.0 45.0 138 hypothetical protein 668 4168612714 612418 297 gp: AF073300_1 Mycobacterium smegmatis 64.9 88.3 94regulatory protein whiB3 669 4169 613156 613719 564 sp: Y09F_MYCTUMycobacterium tuberculosis 55.2 81.6 174 RNA polymerase sigma factorH37Rv Rv3414c sigD 670 4170 613722 614747 1026 671 4171 615180 614803378 sp: Y09H_MYCLE Mycobacterium leprae 41.4 69.8 116 hypotheticalprotein B1620_F3_131 672 4172 615336 616853 1518 gp: AB003154_1Corynebacterium 80.8 93.9 504 IMP dehydrogenase ammoniagenes ATCC 6872guaB 673 4173 616231 615605 627 PIR: F71456 Pyrococcus horikoshii PH030839.0 53.0 146 hypothetical protein 674 4174 616973 618094 1122 gp:AB003154_2 Corynebacterium 70.9 86.1 381 IMP dehydrogenase ammoniagenesATCC 6872 675 4175 619013 618093 921 sp: YBIF_ECOLI Escherichia coli K12ybiF 38.0 67.5 274 hypothetical membrane protein 676 4176 619086 619994909 prf: 1516239A Bacillus subtilis gltC 29.0 58.4 262 glutamatesynthetase positive regulator 677 4177 620004 621572 1569 sp: GUAA_CORAMCorynebacterium 81.6 92.8 517 GMP synthetase ammoniagenes guaA 678 4178620926 620264 663 679 4179 621717 622157 441 680 4180 622269 622457 189681 4181 623635 622460 1176 gp: SCD63_22 Streptomyces coelicolor A3(2)20.5 39.6 513 hypothetical membrane protein 682 4182 623800 624939 1140gp: SC6E10_15 Streptomyces coelicolor A3(2) 26.8 48.7 411 two-componentsystem sensor SC6E10.15c histidine kinase 683 4183 624985 625674 690 sp:DEGU_BACSU Bacillus subtilis 168 degU 33.5 65.1 218 transcriptionalregulator or extracellular proteinase response regulator 684 4184 625677626000 324 685 4185 626558 626070 489 686 4186 627539 626577 963 6874187 627727 628551 825 pir: B70975 Mycobacterium tuberculosis 30.9 64.2201 hypothetical protein H37Rv Rv3395c 688 4188 628551 630140 1590 pir:A70975 Mycobacterium tuberculosis 37.5 64.1 563 hypothetical proteinH37Rv Rv3394c 689 4189 630810 630151 660 690 4190 630949 631809 861 gp:SC5B8_20 Streptomyces coelicolor A3(2) 33.8 62.9 275 hypotheticalprotein SC5B8.20c 691 4191 632684 631824 861 gp: AE001935_7 Deinococcusradiodurans 27.8 58.3 288 hypothetical membrane protein DR0809 692 4192633079 632690 390 693 4193 633474 633079 396 gp: MMU92075_3Mycobacterium marinum 36.8 67.4 95 hypothetical membrane protein 6944194 635175 633532 1644 gp: AF139916_3 Brevibacterium linens ATCC 50.476.2 524 phytoene desaturase 9175 crtl 695 4195 636089 635178 912 gp:AF139916_2 Brevibacterium linens ATCC 42.0 71.2 288 phytoene synthase9175 crtB 696 4196 638278 636089 2190 gp: SCF43A_29 Streptomycescoelicolor A3(2) 48.6 75.6 722 transmembrane transport proteinSCF43A.29c 697 4197 639462 638317 1146 gp: AF139916_11 Brevibacteriumlinens crtE 32.7 63.8 367 geranylgeranyl pyrophosphate (GGPP) synthase698 4198 639624 640208 585 gp: AF139916_14 Brevibacterium linens 38.368.1 188 transcriptional regulator (MarR family) 699 4199 640879 640232648 sp: BLC_CITFR Citrobacter freundii blc OS60 blc 33.1 62.1 145 outermembrane lipoprotein 700 4200 641133 642557 1425 gp: AF139916_1Brevibacterium linens 48.7 74.2 462 hypothetical protein 701 4201 643959642556 1404 gp: AF139916_5 Brevibacterium linens ATCC 40.0 63.2 497 DNAphotolyase 9175 cpd1 702 4202 644026 644778 753 gp: AF155804_7Streptococcus suis cps1K 25.9 53.7 205 glycosyl transferase 703 4203647590 645176 2415 gp: SCE25_30 Streptomyces coelicolor A3(2) 24.3 54.9897 ABC transporter SCE25.30 704 4204 648309 647593 717 prf: 2420410PBacillus subtilis 168 yvrO 35.4 72.2 223 ABC transporter 705 4205 648467648315 153 706 4206 649105 648440 666 prf: 2320284D Helicobacter pyloriabcD 35.9 75.2 206 ABC transporter 707 4207 649342 650187 846 708 4208650193 649114 1080 sp: ABC_ECOLI Escherichia coli TAP90 abc 43.6 75.4346 ABC transporter 709 4209 651288 650392 897 sp: HLPA_HAEINHaemophilus influenzae 28.7 67.2 268 lipoprotein SEROTYPE B hlpA 7104210 651601 654612 3012 prf: 2517386A Thermus aquaticus dnaE 30.2 57.51101 DNA polymerase III 711 4211 654676 655122 447 gp: SCE126_11Streptomyces coelicolor A3(2) 41.5 62.3 159 hypothetical proteinSCE126.11 712 4212 655122 656534 1413 gp: SCE9_1 Streptomyces coelicolorA3(2) 26.1 56.0 468 hypothetical membrane protein SCE9.01 713 4213655834 655097 738 714 4214 656547 657215 669 pir: C70884 Mycobacteriumtuberculosis 50.3 76.4 203 transcriptional repressor H37Rv Rv2788 sirR715 4215 658002 657205 798 gp: SCG8A_5 Streptomyces coelicolor A3(2)34.9 61.7 264 hypothetical protein SCG8A.05c 716 4216 658005 658142 138717 4217 658155 658928 774 pir: C69459 Archaeoglobus fulgidus AF167642.5 71.8 245 transcriptional regulator (Sir2 family) 718 4218 658933659424 492 gp: SC5H1_34 Streptomyces coelicolor A3(2) 45.2 78.3 157hypothetical protein SC5H1.34 719 4219 659543 660538 996 gp: CDU02617_1Corynebacterium diphtheriae 31.1 62.2 357 iron-regulated lipoproteinprecursor irp1 720 4220 661120 660650 471 pir: E70971 Mycobacteriumtuberculosis 62.9 86.1 151 rRNA methylase H37Rv Rv3366 spoU 721 4221661166 662017 852 pir: C70970 Mycobacterium tuberculosis 70.9 87.4 278methylenetetrahydrofolate H37Rv Rv3356c folD dehydrogenase 722 4222662120 662374 255 gp: MLCB1779_8 Mycobacterium leprae 31.3 76.3 80hypothetical membrane protein MLCB1779.16c 723 4223 663761 662382 1380gp: SC66T3_18 Streptomyces coelicolor A3(2) 34.0 63.2 489 hypotheticalprotein SC66T3.18c 724 4224 665088 664126 963 725 4225 666313 6651831131 gp: AF052652_1 Corynebacterium glutamicum 99.5 99.5 379 homoserineO-acetyltransferase metA 726 4226 667770 666460 1311 prf: 2317335ALeptospira meyeri metY 49.7 76.2 429 O-acetylhomoserine sulfhydrylase727 4227 668264 670465 2202 sp: CSTA_ECOLI Escherichia coli K12 cstA53.9 78.4 690 carbon starvation protein 728 4228 670053 669445 609 7294229 670472 670672 201 sp: YJIX_ECOLI Escherichia coli K12 yjiX 40.066.0 50 hypothetical protein 730 4230 671653 671045 609 731 4231 671700672653 954 pir: C70539 Mycobacterium tuberculosis 71.0 86.4 317hypothetical protein H37Rv Rv1130 732 4232 672665 673576 912 prf:1902224A Streptomyces hygroscopicus 41.6 76.2 281 carboxyphosphoenolpyruvate mutase 733 4233 673608 674756 1149 sp: CISY_MYCSMMycobacterium smegmatis 56.1 81.3 380 citrate synthase ATCC 607 gltA 7344234 673639 672710 930 735 4235 674990 674799 192 sp: YNEC_ECOLIEscherichia coli K12 yneC 34.0 62.3 53 hypothetical protein 736 4236675175 675846 672 737 4237 676122 675082 1041 sp: MDH_METFEMethanothermus fervidus V24S 37.6 67.5 338 L-malate dehydrogenase mdh738 4238 676937 676218 720 prf: 2514353L Bacillus stearothermophilus T-626.1 62.8 226 regulatory protein uxuR 739 4239 677748 677047 702 7404240 681027 680131 897 sp: VIUB_VIBCH Vibrio cholerae OGAWA 395 25.454.2 284 vibriobactin utilization protein viuB 741 4241 681846 681040807 gp: AF176902_3 Corynebacterium diphtheriae 55.4 85.1 269 ABCtransporter ATP-binding protein irp1D 742 4242 682904 681846 1059 gp:AF176902_2 Corynebacterium diphtheriae 56.3 86.4 339 ABC transporterirp1C 743 4243 683866 682871 996 gp: AF176902_1 Corynebacteriumdiphtheriae 63.0 88.2 330 ABC transporter irp1B 744 4244 684925 6838761050 gp: CDU02617_1 Corynebacterium diphtheriae 53.1 82.3 356iron-regulated lipoprotein precursor irp1 745 4245 685109 686380 1272prf: 2202262A Streptomyces venezuelae cmlv 32.2 69.6 395 chloramphenicolresistance protein 746 4246 686435 687346 912 prf: 2222220B Pseudomonasaeruginosa crc 30.4 58.1 303 catabolite repression control protein 7474247 687351 688007 657 sp: YICG_HAEIN Haemophilus influenzae Rd 56.285.8 219 hypothetical protein HI1240 748 4248 688141 688335 195 749 4249689890 688916 975 750 4250 690696 689917 780 gp: AF109162_3Corynebacterium diphtheriae 45.1 73.8 244 ferrichrome ABC transporterhmuV 751 4251 691722 690706 1017 pir: S54438 Yersinia enterocoliticahemU 38.7 69.1 346 hemin permease 752 4252 691882 692916 1035 sp:SYW_ECOLI Escherichia coli K12 trpS 54.4 79.8 331 tryptophanyl-tRNAsynthetase 753 4253 693028 694110 1083 sp: YHJD_ECOLI Escherichia coliK12 yhjD 37.1 72.3 278 hypothetical protein 754 4254 694172 695074 903755 4255 696213 695077 1137 sp: DACD_SALTY Salmonella typhimurium LT230.9 57.5 301 penicillin-binding protein 6B dacD precursor 756 4256697995 696769 1227 pir: F70842 Mycobacterium tuberculosis 34.1 70.7 417hypothetical protein H37Rv Rv3311 757 4257 698922 698065 858 gp:SC6G10_8 Streptomyces coelicolor A3(2) 29.4 52.6 323 hypotheticalprotein SC6G10.08c 758 4258 699072 699266 195 759 4259 699272 698922 351760 4260 699281 699913 633 sp: UPP_LACLA Lactococcus lactis upp 46.472.3 209 uracil phosphoribosyltransferase 761 4261 699998 700381 384 gp:SC1A2_11 Streptomyces coelicolor A3(2) 41.6 66.2 77 bacterial regulatoryprotein, lacl SC1A2.11 family 762 4262 702081 703262 1182 pir: H70841Mycobacterium tuberculosis 51.4 80.5 385 N-acyl-L-amino acidamidohydrolase H37Rv Rv3305c amiA or peptidase 763 4263 702108 7003841725 sp: MANB_MYCPI Mycoplasma pirum BER manB 22.1 53.8 561phosphomannomutase 764 4264 703405 704811 1407 sp: DLDH_HALVOHalobacterium volcanii ATCC 31.6 65.0 468 dihydrolipoamide dehydrogenase29605 lpd 765 4265 705211 708630 3420 prf: 2415454A Corynebacteriumglutamicum 100.0 100.0 1140 pyruvate carboxylase strain21253 pyc 7664266 708839 709708 870 sp: YD24_MYCTU Mycobacterium tuberculosis 26.260.1 263 hypothetical protein H37Rv Rv1324 767 4267 709793 710278 486gp: SCF11_30 Streptomyces coelicolor A3(2) 30.7 66.9 127 hypotheticalprotein SCF11.30 768 4268 711605 710520 1086 pir: B69760 Bacillussubtilis 168 yciC 44.6 69.0 381 hypothetical protein 769 4269 711724712647 924 sp: TRXB_BACSU Bacillus subtilis IS58 trxB 24.6 59.3 305thioredoxin reductase 770 4270 712738 714231 1494 sp: PRPD_SALTYSalmonella typhimurium LT2 24.0 49.5 521 PrpD protein for propionateprpD catabolism 771 4271 714258 715145 888 prf: 1902224A Streptomyceshygroscopicus 42.5 74.5 278 carboxy phosphoenolpyruvate mutase 772 4272714757 714380 378 PIR: E72779 Aeropyrum pernix K1 APE0223 39.0 47.0 96hypothetical protein 773 4273 715102 716283 1182 sp: CISY_MYCSMMycobacterium smegmatis 54.6 78.9 383 citrate synthase ATCC 607 gltA 7744274 716660 716286 375 775 4275 718009 716687 1323 pir: B70539Mycobacterium tuberculosis 40.8 72.6 456 hypothetical protein H37RvRv1129c 776 4276 718105 718350 246 777 4277 718658 720016 1359 778 4278721449 720547 903 sp: THTR_CORGL Corynebacterium glutamicum 100.0 100.0225 thiosulfate sulfurtransferase ATCC 13032 thtR 779 4279 721777 7228411065 gp: CJ11168X1_62 Campylobacter jejuni Cj0069 61.1 79.8 352hypothetical protein 780 4280 723338 722925 414 gp: MLCB4_16Mycobacterium leprae 51.1 76.7 133 hypothetical protein MLCB4.27c 7814281 723412 725559 2148 pir: G70539 Mycobacterium tuberculosis 35.1 63.4718 hypothetical membrane protein H37Rv Rv1565c 782 4282 726462 725872591 sp: YCEF_ECOLI Escherichia coli K12 yceF 31.8 66.2 192 hypotheticalprotein 783 4283 726715 726470 246 prf: 2323363CF Mycobacterium lepraeB1308- 33.3 69.8 63 hypothetical protein C3-211 784 4284 728352 7267421611 gp: AB018531_2 Corynebacterium glutamicum 99.8 100.0 537 detergentsensitivity rescuer or AJ11060 dtsR2 carboxyl transferase 785 4285730324 728696 1629 pir: JC4991 Corynebacterium glutamicum 99.6 100.0 543detergent sensitivity rescuer or AJ11060 dtsR1 carboxyl transferase 7864286 730436 731299 864 sp: BIRA_ECOLI Escherichia coli K12 birA 28.761.8 293 bifunctional protein (biotin synthesis repressor and biotinacetyl-CoA carboxylase ligase) 787 4287 731312 731797 486 pir: G70979Mycobacterium tuberculosis 23.0 58.8 165 hypothetical membrane proteinH37Rv Rv3278c 788 4288 731857 733017 1161 sp: PURK_CORAM Corynebacterium69.0 83.8 394 5′-phosphoribosyl-5-amino-4- ammoniagenes ATCC 6872imidasol carboxylase purK 789 4289 733072 734943 1872 sp: KUP_ECOLIEscherichia coli K12 kup 41.1 73.6 628 K+-uptake protein 790 4290 733797733183 615 791 4291 734984 735340 357 792 4292 735402 735896 495 sp:PUR6_CORAM Corynebacterium 85.7 93.2 147 5′-phosphoribosyl-5-amino-4-ammoniagenes ATCC 6872 imidasol carboxylase purE 793 4293 735899 736351453 gp: APU33059_5 Actinosynnema pretiosum 36.2 60.5 152 hypotheticalprotein 794 4294 736413 737204 792 gp: SCF43A_36 Streptomyces coelicolorA3(2) 42.8 70.6 255 hypothetical protein SCF43A.36 795 4295 738529737216 1314 sp: NTAA_CHEHE Chelatobacter heintzii ATCC 43.2 73.0 426nitrilotriacetate monooxygenase 29600 ntaA 796 4296 740172 738673 1500pir: A69426 Archaeoglobus fulgidus 23.4 52.5 303 transposase (ISA0963-5)797 4297 741016 740228 789 sp: DHG2_BACME Bacillus megaterium IAM 103031.3 64.8 256 glucose 1-dehydrogenase gdhII 798 4298 741397 741765 369pir: A72258 Thermotoga maritima MSB8 29.2 68.8 96 hypothetical membraneprotein TM1408 799 4299 741854 742195 342 800 4300 742384 741818 567 sp:YWJB_BACSU Bacillus subtilis 168 ywjB 28.6 66.3 175 hypothetical protein801 4301 742409 742828 420 gp: SCJ9A_21 Streptomyces coelicolor A3(2)35.9 76.8 142 hypothetical protein SCJ9A.21 802 4302 743052 742831 222803 4303 743900 743067 834 prf: 2406355C Thermococcus litoralis malG42.4 75.3 271 trehalose/maltose-binding protein 804 4304 744931 7439001032 prf: 2406355B Thermococcus litoralis malF 37.3 70.3 306trehalose/maltose-binding protein 805 4305 745513 745046 468 806 4306746893 745622 1272 prf: 2406355A Thermococcus litoralis malE 30.9 62.4417 trehalose/maltose-binding protein 807 4307 748020 748442 423 8084308 748026 747031 996 prf: 2308356A Streptomyces reticuli msiK 57.273.9 332 ABC transporter ATP-binding protein (ABC-type sugar transportprotein) or celloblose/maltose transport protein 809 4309 748446 748814369 810 4310 753685 748886 4800 pir: B75633 Deinococcus radiodurans R125.1 49.9 1783 RNA helicase DRB0135 811 4311 757063 757434 372 812 4312757395 753697 3699 813 4313 758262 757630 633 pir: E70978 Mycobacteriumtuberculosis 31.7 59.2 240 hypothetical protein H37Rv Rv3268 814 4314760796 758364 2433 pir: C71929 Helicobacter pylori J99 jhp0462 30.0 62.5720 hypothetical protein 815 4315 762468 760906 1563 sp: UVRD_ECOLIEscherichia coli K12 uvrD 20.7 41.1 701 DNA helicase II 816 4316 762497762853 357 817 4317 762730 763122 393 818 4318 762977 762582 396 8194319 768191 767367 825 820 4320 769443 763237 6207 pir: T36671Streptomyces coelicolor 22.4 45.8 2033 RNA helicase SCH5.13 821 4321774142 769547 4596 pir: T08313 Halobacterium sp. NRC-1 24.4 53.2 698hypothetical protein plasmid pNRC100 H1130 822 4322 777035 774150 2886sp: HEPA_ECOLI Escherichia coli K12 hepA 23.1 48.6 873 RNA polymeraseassociated protein (ATP-dependent helicase) 823 4323 778711 777158 1554pir: D70978 Mycobacterium tuberculosis 45.5 71.4 527 hypotheticalprotein H37Rv Rv3267 824 4324 779014 779910 897 gp: AF187550_1Mycobacterium smegmatis 56.4 77.9 289 dTDP-Rha: a-D-GlcNAc- mc2155 wbbLdiphosphoryl polyprenol, a-3-L- rhamnosyl transferase 825 4325 780128781171 1044 sp: MPG1_YEAST Saccharomyces cerevisiae 29.8 66.9 353mannose-1-phosphate YDL055C MPG1 guanylyltransferase 826 4326 781468781875 408 gp: AF164439_1 Mycobacterium smegmatis 73.4 81.9 94regulatory protein whmD 827 4327 782617 782162 456 pir: B70847Mycobacterium tuberculosis 48.9 74.8 139 hypothetical protein H37RvRv3259 828 4328 782712 783101 390 gp: SCE34_11 Streptomyces coelicolorA3(2) 51.5 71.3 136 hypothetical protein SCE34.11c 829 4329 783184784557 1374 sp: MANB_SALMO Salmonella montevideo M40 38.0 66.3 460phosphomannomutase manB 830 4330 784635 785639 1005 pir: B70594Mycobacterium tuberculosis 31.2 56.3 327 hypothetical protein H37RvRv3256c 831 4331 785643 786824 1182 sp: MANA_ECOLI Escherichia coli K12manA 36.9 66.2 420 mannose-6-phosphate isomerase 832 4332 786896 787045150 833 4333 787624 787983 360 834 4334 787733 787170 564 prf: 1804279KEnterococcus faecalis plasmid 35.6 57.8 180 pheromone-responsive proteinpCF10 prgC 835 4335 788196 788546 351 836 4336 788672 790093 1422 sp:SAHH_TRIVA Trichomonas vaginalis WAA38 59.0 83.0 476S-adenosyl-L-homocysteine hydrolase 837 4337 789426 788719 708 838 4338789721 789002 720 839 4339 790096 790704 609 sp: KTHY_ARCFUArchaeoglobus fulgidus VC-16 25.8 56.0 209 thymidylate kinase AF0061 8404340 790732 791409 678 prf: 2214304A Mycobacterium tuberculosis 73.790.6 224 two-component system response H37Rv Rv3246c mtrA regulator 8414341 791421 790738 684 842 4342 791512 793008 1497 prf: 2214304BMycobacterium tuberculosis 53.1 78.9 484 two-component system sensorH37Rv Rv3245c mtrB histidine kinase 843 4343 793008 794711 1704 pir:F70592 Mycobacterium tuberculosis 29.6 65.6 595 lipoprotein H37RvRv3244c lpqB 844 4344 794714 795301 588 pir: D70592 Mycobacteriumtuberculosis 38.0 72.8 213 hypothetical protein H37Rv Rv3242c 845 4345795447 795292 156 846 4346 795448 796110 663 sp: RR30_SPIOL Spinaciaoleracea CV rps22 34.5 61.6 203 30S ribosomal protein or chloroplastprecursor 847 4347 796250 798784 2535 gsp: R74093 Brevibacterium flavum99.1 99.6 845 preprotein translocase SecA subunit (Corynebacteriumglutamicum) MJ-233 secA 848 4348 799020 799691 672 849 4349 799697800200 504 pir: A70591 Mycobacterium tuberculosis 47.1 78.8 170hypothetical protein H37Rv Rv3231c 850 4350 801194 800208 987 pir:F70590 Mycobacterium tuberculosis 64.6 82.9 322 hypothetical proteinH37Rv Rv3228 851 4351 802602 801190 1413 gp: AF114233_1 Corynebacteriumglutamicum 99.0 99.0 461 5-enolpyruvylshikimate 3-phosphate ASO19 aroAsynthase 852 4352 802649 803128 480 pir: D70590 Mycobacteriumtuberculosis 38.3 63.9 180 hypothetical protein H37Rv Rv3226c 853 4353802687 802565 123 GP: AF114233_1 Corynebacterium glutamicum 100.0 100.023 5-enolpyruvylshikimate 3-phosphate synthase 854 4354 804240 8031311110 pir: G70506 Mycobacterium tuberculosis 21.6 42.4 380 hypotheticalprotein H37Rv Rv0336 855 4355 804408 805025 618 prf: 2515333DMycobacterium tuberculosis 61.2 87.2 188 RNA polymerase sigma factorsigH 856 4356 805792 805535 258 pir: D70596 Mycobacterium tuberculosis78.6 96.4 84 regulatory protein H37Rv Rv3219 whiB1 857 4357 806318806737 420 pir: B70596 Mycobacterium tuberculosis 33.3 65.1 129hypothetical protein H37Rv Rv3217c 858 4358 807939 806740 1200 pir:E70595 Mycobacterium tuberculosis 29.6 62.2 415 hypothetical proteinH37Rv Rv3212 859 4359 809217 807946 1272 sp: DEAD_KLEPN Klebsiellapneumoniae CG43 37.3 64.0 458 DEAD box ATP-dependent RNA deaD helicase860 4360 809286 809510 225 861 4361 809549 810394 846 pir: H70594Mycobacterium tuberculosis 46.4 69.8 291 hypothetical protein H37RvRv3207c 862 4362 810405 811163 759 pir: F70594 Mycobacteriumtuberculosis 37.0 65.9 249 hypothetical protein H37Rv Rv3205c 863 4363811170 814217 3048 pir: G70951 Mycobacterium tuberculosis 23.9 48.9 1155ATP-dependent DNA helicase H37Rv Rv3201c 864 4364 812165 811386 780 8654365 814204 817422 3219 pir: G70951 Mycobacterium tuberculosis 41.4 65.71126 ATP-dependent DNA helicase H37Rv Rv3201c 866 4366 815541 8142101332 867 4367 817519 818523 1005 sp: Y13B_METJA Methanococcus jannaschiiJAL- 26.2 64.2 302 potassium channel 1 MJ0138.1. 868 4368 818523 819236714 pir: E70951 Mycobacterium tuberculosis 30.4 58.3 230 hypotheticalprotein H37Rv Rv3199c 869 4369 819254 821287 2034 sp: UVRD_ECOLIEscherichia coli K12 uvrD 32.6 58.8 660 DNA helicase II 870 4370 822079822669 591 871 4371 822105 821290 816 pir: B70951 Mycobacteriumtuberculosis 26.8 49.3 280 hypothetical protein H37Rv Rv3196 872 4372822789 823391 603 873 4373 824125 822680 1446 pir: A70951 Mycobacteriumtuberculosis 42.8 76.4 474 hypothetical protein H37Rv Rv3195 874 4374824190 825239 1050 pir: H70950 Mycobacterium tuberculosis 43.4 74.9 350hypothetical protein H37Rv Rv3194 875 4375 825916 825242 675 876 4376826517 825996 522 877 4377 826616 829570 2955 pir: G70950 Mycobacteriumtuberculosis 47.2 73.5 1023 hypothetical protein H37Rv Rv3193c 878 4378830985 829627 1359 gp: AE001938_5 Deinococcus radiodurans 34.3 57.7 463regulatory protein DR0840 879 4379 831021 831971 951 sp: ER1_HEVBR Heveabrasiliensis laticifer er1 67.4 89.0 301 ethylene-inducible protein 8804380 831922 831578 345 PIR: F72782 Aeropyrum pernix K1 APE0247 49.0 53.081 hypothetical protein 881 4381 831971 832570 600 sp: YAAE_BACSUBacillus subtilis 168 yaaE 40.8 73.6 201 hypothetical protein 882 4382833157 832795 363 883 4383 833572 834633 1062 pir: TRYXB4 Lysobacterenzymogenes ATCC 26.7 44.4 408 alpha-lytic proteinase precursor 29487884 4384 834888 835388 501 885 4385 835253 835837 585 pir: S03722Neurospora intermedia LaBelle- 25.0 51.4 208 DNA-directed DNA polymerase1b mitochondrion plasmid 886 4386 837312 838892 1581 sp: CSP1_CORGLCorynebacterium glutamicum 27.0 51.5 363 major secreted protein PS1protein (Brevibacterium flavum) ATCC precursor 17965 csp1 887 4387838925 839353 429 888 4388 839630 840139 510 889 4389 840431 840210 222890 4390 840745 840437 309 891 4391 842296 841517 780 prf: 2207273HStreptomyces alboniger pur3 51.8 74.9 255 monophosphatase 892 4392843124 842306 819 gp: U70376_9 Streptomyces flavopersicus 33.7 59.3 243myo-inositol monophosphatase spcA 893 4393 843257 844360 1104 sp:RF2_STRCO Streptomyces coelicolor A3(2) 68.0 88.6 359 peptide chainrelease factor 2 prfB 894 4394 844495 845181 687 pir: E70919Mycobacterium tuberculosis 70.4 91.2 226 cell division ATP-bindingprotein H37Rv Rv3102c ftsE 895 4395 845105 844842 264 PIR: G72510Aeropyrum pernix K1 APE2061 43.0 54.0 72 hypothetical protein 896 4396845198 846097 900 pir: D70919 Mycobacterium tuberculosis 40.5 74.8 301cell division protein H37Rv Rv3101c ftsX 897 4397 846137 846628 492 sp:SMPB_ECOLI Escherichia coli K12 smpB 43.5 75.9 145 small protein B(SSRA-binding protein) 898 4398 846632 846982 351 sp: YEAO_ECOLIEscherichia coli K12 yeaO 44.0 73.3 116 hypothetical protein 899 4399846805 846269 537 900 4400 847727 848026 300 901 4401 848122 847718 405902 4402 849323 848499 825 sp: VIUB_VIBCH Vibrio cholerae OGAWA 395 26.852.9 272 vibriobactin utilization protein viuB 903 4403 850243 849326918 prf: 2510361A Staphylococcus aureus sirA 29.5 58.3 319 Fe-regulatedprotein 904 4404 850999 850412 588 gp: MLCB1243_5 Mycobacterium leprae36.1 71.2 191 hypothetical membrane protein MLCB1243.07 905 4405 851351852364 1014 sp: FATB_VIBAN Vibrio anguillarum 775 fatB 27.7 61.5 325ferric anguibactin-binding protein precursor 906 4406 852618 853616 999pir: B69763 Bacillus subtilis 168 yclN 39.3 80.8 313 ferrichrome ABCtransporter (permease) 907 4407 853783 854724 942 pir: C69763 Bacillussubtilis 168 yclO 35.6 76.0 312 ferrichrome ABC transporter (permease)908 4408 854724 855476 753 pir: D69763 Bacillus subtilis 168 yclP 48.482.0 250 ferrichrome ABC transporter (ATP- binding protein) 909 4409860224 860078 147 PIR: F81737 Chlamydia muridarum Nigg 66.0 72.0 48hypothetical protein TC0129 910 4410 860745 860473 273 GSP: Y35814Chlamydia pneumoniae 61.0 66.0 84 hypothetical protein 911 4411 861544862752 1209 pir: S66270 Rattus norvegicus (Rat) 33.5 64.9 442 kynurenineaminotransferase/glutamine transaminase K 912 4412 863391 862753 639 9134413 865066 863396 1671 sp: RA25_YEAST Saccharomyces cerevisiae 30.762.3 613 DNA repair helicase S288C YIL143C RAD25 914 4414 867317 8651192199 pir: F70815 Mycobacterium tuberculosis 36.1 65.2 764 hypotheticalprotein H37Rv Rv0862c 915 4415 867353 867571 219 pir: G70815Mycobacterium tuberculosis 44.0 62.0 57 hypothetical protein H37RvRv0863 916 4416 867788 868630 843 917 4417 868399 867803 597 prf:2420502A Micrococcus luteus rpf 39.4 64.7 198 resuscitation-promotingfactor 918 4418 868938 869318 381 prf: 2320271A Lactococcus lactis cspB42.6 75.4 61 cold shock protein 919 4419 869903 869379 525 gp: MLCB57_11Mycobacterium leprae 28.3 58.5 159 hypothetical protein MLCB57.27c 9204420 870691 869918 774 gp: AE001874_1 Deinococcus radiodurans 41.8 67.8273 glutamine cyclotransferase DR0112 921 4421 871419 870721 699 9224422 871523 871660 138 923 4423 871738 873210 1473 gp: SC6C5_9Streptomyces coelicolor A3(2) 43.6 79.3 477 permease SC6C5.09 924 4424872927 872016 912 925 4425 873213 874040 828 sp: TSNR_STRAZ Streptomycesazureus tsnR 27.9 51.7 319 rRNA(adenosine-2′-O-)- methyltransferase 9264426 874944 874069 876 927 4427 875883 874951 933 sp: YZ11_MYCTUMycobacterium tuberculosis 32.6 55.1 316 hypothetical protein H37RvRv0883c 928 4428 877112 875985 1128 pir: S71439 Bacillus circulans ATCC21783 21.9 52.9 374 phosphoserine transaminase 929 4429 881114 8796421473 sp: ACCD_ECOLI Escherichia coli K12 accD 36.0 69.5 236acetyl-coenzyme A carboxylase carboxy transferase subunit beta 930 4430881647 881985 339 gp: SCI8_8 Streptomyces coelicolor A3(2) 51.5 80.6 103hypothetical protein SCI8.08c 931 4431 881995 883647 1653 pir: JC2382Pseudomonas fluorescens 26.4 58.1 549 sodium/proline symporter 932 4432883726 884541 816 933 4433 885388 884549 840 pir: A70657 Mycobacteriumtuberculosis 49.0 77.4 243 hypothetical protein H37Rv Rv2525c 934 4434885672 894578 8907 pir: S55505 Corynebacterium 63.1 83.4 3026 fatty-acidsynthase ammoniagenes fas 935 4435 894703 895191 489 936 4436 895408895593 186 937 4437 896642 895596 1047 prf: 2317335B Leptospira meyerimetX 29.0 59.7 335 homoserine O-acetyltransferase 938 4438 897144 896719426 939 4439 897423 897689 267 940 4440 897963 897727 237 gp: AE002044_8Deinococcus radiodurans 43.6 72.6 62 glutaredoxin DR2085 941 4441 898434897979 456 prf: 2408256A Mycobacterium avium folA 38.0 62.0 171dihydrofolate reductase 942 4442 899231 898434 798 sp: TYSY_ECOLIEscherichia coli K12 thyA 64.8 88.9 261 thymidylate synthase 943 4443900008 899253 756 sp: CYSQ_ECOLI Escherichia coli K12 cysQ 32.2 56.4 202ammonium transporter 944 4444 900043 904602 4560 gp: SC7C7_16Streptomyces coelicolor A3(2) 47.4 68.1 1715 ATP dependent DNA helicaseSC7C7.16c 945 4445 904615 905382 768 sp: FPG_SYNEN Synechococcuselongatus 29.2 51.0 298 formamidopyrimidine-DNA naegeli mutM glycosidase946 4446 905389 905796 408 pir: F70816 Mycobacterium tuberculosis 55.586.7 128 hypothetical protein H37Rv Rv0870c 947 4447 906391 905792 600sp: APL_LACLA Lactococcus lactis MG1363 apl 38.8 71.9 196 alkalinephosphatase 948 4448 907731 906559 1173 pir: T36776 Streptomycescoelicolor A3(2) 33.8 67.0 403 integral membrane transporter SCI28.06c949 4449 908612 909328 717 950 4450 909378 907759 1620 pir: NUECEscherichia coli JM101 pgi 52.4 77.0 557 glucose-6-phosphate isomease951 4451 910696 909521 1176 pir: G70506 Mycobacterium tuberculosis 24.652.3 195 hypothetical protein H37Rv Rv0336 952 4452 910843 911223 381953 4453 911163 910855 309 sp: YT26_MYCTU Mycobacterium tuberculosis59.0 85.9 78 hypothetical protein H37Rv Rv0948c 954 4454 911226 9135142289 sp: PCRA_BACST Bacillus stearothermophilus 46.1 73.1 763ATP-dependent helicase NCA 1503 pcrA 955 4455 915699 913477 2223 gp:SCE25_30 Streptomyces coelicolor A3(2) 21.8 48.6 885 ABC transporterSCE25.30 956 4456 916364 915699 666 prf: 2420410P Bacillus subtilis 168yvrO 43.8 71.4 217 ABC transporter 957 4457 916874 916368 507 958 4458917680 916970 711 pir: D70716 Mycobacterium tuberculosis 43.6 73.3 236peptidase H37Rv Rv0950c 959 4459 917928 919352 1425 sp: YT19_MYCTUMycobacterium tuberculosis 31.1 60.8 434 hypothetical protein H37RvRv0955 960 4460 918054 917827 228 961 4461 919330 919956 627 gp:AB003159_2 Corynebacterium 64.6 86.2 189 5′-phosphoribosylglycinamideammoniagenes purN formyltransferase 962 4462 919967 921526 1560 gp:AB003159_3 Corynebacterium 74.5 87.8 5255′-phosphoribosyl-5-aminoimidazole- ammoniagenes purH 4-carboxamideformyltransferase 963 4463 921594 922412 819 gp: CGL133719_3Corynebacterium glutamicum 100.0 100.0 217 citrate lyase (subunit) ATCC13032 citE 964 4464 923061 922396 666 gp: CGL133719_2 Corynebacteriumglutamicum 100.0 100.0 222 repressor of the high-affinity (methyl) ATCC13032 amtR ammonium uptake system 965 4465 923464 923138 327 gp:CGL133719_1 Corynebacterium glutamicum 100.0 100.0 109 hypotheticalprotein ATCC 13032 yjcC 966 4466 923661 923981 321 967 4467 924407924159 249 sp: RR18_CYAPA Cyanophora paradoxa rps18 52.2 76.1 67 30Sribosomal protein S18 968 4468 924727 924425 303 sp: RS14_ECOLIEscherichia coli K12 rpsN 54.0 80.0 100 30S ribosomal protein S14 9694469 924895 924734 162 sp: RL33_ECOLI Escherichia coli K12 rpmG 55.183.7 49 50S ribosomal protein L33 970 4470 925134 924901 234 pir: R5EC28Escherichia coli K12 rpmB 52.0 81.8 77 50S ribosomal protein L28 9714471 926935 925325 1611 pir: B70033 Bacillus subtilis 168 yvdB 34.4 71.1529 transporter (sulfate transporter) 972 4472 927242 926931 312 prf:2420312A Staphylococcus aureus zntR 37.5 77.5 80 Zn/Co transportrepressor 973 4473 927474 927737 264 sp: RL31_HAEDU Haemophilus ducreyirpmE 37.2 65.4 78 50S ribosomal protein L31 974 4474 927752 927922 171gp: SC51A_14 Streptomyces coelicolor A3(2) 60.0 78.2 55 50S ribosomalprotein L32 SCF51A.14 975 4475 927785 927339 447 976 4476 928117 928812696 sp: COPR_PSESM Pseudomonas syringae copR 48.0 73.6 227copper-inducible two-component regulator 977 4477 928884 930248 1365 sp:BAES_ECOLI Escherichia coli K12 baeS 24.4 60.1 484 two-component systemsensor 978 4478 930410 931648 1239 pir: S45229 Escherichia coli K12 htrA33.3 59.9 406 proteinase DO precursor 979 4479 931706 932290 585 sp:CNX1_ARATH Arabidopsis thaliana CV cnx1 27.7 54.3 188 molybdopterinbiosynthesis cnx1 protein (molybdenum cofactor biosynthesis enzyme cnx1)980 4480 932290 932487 198 981 4481 932974 932570 405 sp: MSCL_MYCTUMycobacterium tuberculosis 50.4 77.1 131 large-conductance H37Rv Rv0985cmscL mechanosensitive channel 982 4482 933710 933060 651 pir: A70601Mycobacterium tuberculosis 28.6 60.0 210 hypothetical protein H37RvRv0990 983 4483 934302 933733 570 pir: JC4389 Homo sapiens MTHFS 25.159.7 191 5-formyltetrahydrofolate cyclo-ligase 984 4484 934423 935319897 pir: JC4985 Xanthomonas campestris 42.2 68.9 296UTP—glucose-1-phosphate uridylyltransferase 985 4485 935351 936607 1257prf: 2403296B Arthrobacter nicotinovorans 31.8 62.6 390 molybdopterinbiosynthesis protein moeA 986 4486 936615 937274 660 sp: RIMJ_ECOLIEscherichia coli K12 rimJ 29.0 54.9 193 ribosomal-protein-alanine N-acetyltransferase 987 4487 937382 938401 1020 pir: G70601 Mycobacteriumtuberculosis 30.3 54.8 367 hypothetical membrane protein H37Rv Rv0996988 4488 938427 939626 1200 sp: CYNX_ECOLI Escherichia coli K12 cynX26.6 62.4 380 cyanate transport protein 989 4489 939217 937799 1419 9904490 939686 940090 405 sp: YG02_HAEIN Haemophilus influenzae Rd 32.160.6 137 hypothetical membrane protein HI1602 991 4491 940041 940754 714sp: Y05C_MYCTU Mycobacterium tuberculosis 25.3 59.6 225 hypotheticalmembrane protein H37Rv Rv0093c 992 4492 940759 941925 1167 sp:CDAS_BACSH Bacillus sphaericus E-244 26.8 53.6 444 cyclomaltodextrinaseCDase 993 4493 943940 942381 1560 pir: E70602 Mycobacterium tuberculosis43.0 75.2 488 hypothetical membrane protein H37Rv 994 4494 944009 944833825 sp: Y19J_MYCTU Mycobacterium tuberculosis 54.0 78.3 272 hypotheticalprotein H37Rv Rv1003 995 4495 946840 948669 1830 sp: SYM_METTHMethanobacterium 33.8 66.7 615 methionyl-tRNA synthetasethermoautotrophicum Delta H MTH587 metG 996 4496 948791 950839 2049 prf:1306383A Escherichia coli recQ 26.2 49.0 741 ATP-dependent DNA helicase997 4497 951460 950828 633 pir: B69206 Methanobacterium 27.6 53.3 210hypothetical protein thermoautotrophicum Delta H MTH796 998 4498 952991951834 1158 sp: YXAG_BACSU Bacillus subtilis 168 yxaG 30.0 59.0 363hypothetical protein 999 4499 953573 953043 531 1000 4500 953973 954266294 gp: AF029727_1 Enterococcus faecium 33.0 59.6 94 transposase 10014501 954277 954753 477 pir: TQECI3 Escherichia coli K12 41.7 67.6 139transposase 1002 4502 954941 955354 414 gp: AF052055_1 Brevibacteriumlinens tnpA 73.2 88.4 112 transposase subunit 1003 4503 955911 956774864 1004 4504 957398 955686 1713 prf: 2014253AE Escherichia coli dld46.4 75.6 565 D-lactate dehydrogenase 1005 4505 958683 957844 840 sp:MTK1_KLEPN Klebsiella pneumoniae OK8 30.8 62.8 231 site-specificDNA-methyltransferase kpnIM 1006 4506 959403 959185 219 1007 4507 960081960374 294 gp: AF029727_1 Enterococcus faecium 33.0 59.6 94 transposase1008 4508 960385 960861 477 pir: TQECI3 Escherichia coli K12 41.7 67.6139 transposase 1009 4509 961297 961653 357 sp: YJ94_MYCTU Mycobacteriumtuberculosis 62.6 84.6 91 transcriptional regulator H37Rv Rv1994c 10104510 961629 962249 621 prf: 2514367A Staphylococcus aureus cadD 31.766.8 205 cadmium resistance protein 1011 4511 961662 961321 342 10124512 962809 963639 831 pir: C70603 Mycobacterium tuberculosis 46.4 70.7263 hypothetical protein H37Rv Rv1008 1013 4513 963864 964934 1071 pir:D70603 Mycobacterium tuberculosis 34.8 63.5 362 hypothetical proteinH37Rv Rv1009 rpf 1014 4514 964974 965852 879 sp: KSGA_ECOLI Escherichiacoli K12 ksgA 34.3 65.3 265 dimethyladenosine transferase 1015 4515965852 966784 933 pir: F70603 Mycobacterium tuberculosis 42.5 67.0 315isopentenyl monophosphate kinase H37Rv Rv1011 1016 4516 966591 965950642 1017 4517 966828 968660 1833 pir: S47441 Saccharopolyspora erythraea65.5 85.8 478 ABC transporter ertX 1018 4518 968667 969458 792 sp:PDXK_ECOLI Escherichia coli K12 pdxK 40.1 67.4 242 pyridoxine kinase1019 4519 969940 969461 480 sp: YX05_MYCTU Mycobacterium tuberculosis27.0 58.5 159 hypothetical protein H37Rv Rv2874 1020 4520 970029 970349321 gp: SCF1_2 Streptomyces coelicolor A3(2) 45.4 78.7 108 hypotheticalprotein SCF1.02 1021 4521 970418 970738 321 gp: SCF1_2 Streptomycescoelicolor A3(2) 35.5 69.2 107 hypothetical protein SCF1.02 1022 4522970864 971823 960 gp: SCJ1_15 Streptomyces coelicolor A3(2) 64.8 88.1261 regulator SCJ1.15 1023 4523 973035 972244 792 sp: YXEH_BACSUBacillus subtilis 168 yxeH 27.2 59.1 276 hypothetical protein 1024 4524973139 974155 1017 pir: E70893 Mycobacterium tuberculosis 35.6 70.9 337enoyl-CoA hydratase H37Rv echA9 1025 4525 973957 973304 654 1026 4526974186 974962 777 1027 4527 976176 974965 1212 1028 4528 976349 9777341386 sp: CSP1_CORGL Corynebacterium glutamicum 27.7 56.8 440 majorsecreted protein PS1 protein (Brevibacterium flavum) ATCC precursor17965 csp1 1029 4529 978378 977800 579 gp: SCF56_6 Streptomycescoelicolor A3(2) 44.0 70.0 100 transcriptional regulator (tetR SCF56.06family) 1030 4530 980740 978368 2373 gp: SCE87_17 Streptomycescoelicolor A3(2) 42.6 70.0 802 membrane transport protein SCE87.17c 10314531 980993 981490 498 sp: MENG_HAEIN Haemophilus influenzae Rd 38.275.8 157 S-adenosylmethionine: 2- HI0508 menG demethylmenaquinonemethyltransferase 1032 4532 981622 982287 666 1033 4533 982674 982294381 gp: NMA6Z2491_214 Neisseria meningitidis NMA1953 29.8 63.6 121hypothetical protein 1034 4534 983100 984650 1551 pir: A70539Mycobacterium tuberculosis 24.9 48.3 482 hypothetical protein H37RvRv1128c 1035 4535 984910 985845 936 1036 4536 986510 984864 1647 pir:I59305 Escherichia coli K12 prfC 39.2 68.0 546 peptide-chain-releasefactor 3 1037 4537 986739 988007 1269 prf: 2406311A Methylophilusmethylotrophus 42.8 72.8 404 amide-urea transport protein fmdD 1038 4538988023 988904 882 prf: 2406311B Methylophilus methylotrophus 40.8 61.077 amide-urea transport protein fmdE 1039 4539 988904 989980 1077 prf:2406311C Methylophilus methylotrophus 34.6 68.0 234 amide-urea transportprotein fmdF 1040 4540 989980 990705 726 sp: BRAF_PSEAE Pseudomonasaeruginosa PAO 37.9 70.0 253 high-affinity branched-chain amino braFacid transport ATP-binding protein 1041 4541 990716 991414 699 sp:BRAG_PSEAE Pseudomonas aeruginosa PAO 35.2 69.1 236 high-affinitybranched-chain amino braG acid transport ATP-binding protein 1042 4542992028 991417 612 sp: PTH_ECOLI Escherichia coli K12 pth 39.0 70.6 187peptidyl-tRNA hydrolase 1043 4543 992058 993080 1023 sp: 2NPD_WILMRWilliopsis mrakii IFO 0895 25.2 54.0 361 2-nitropropane dioxygenase 10444544 993549 994613 1065 sp: G3P_ZYMMO Streptomyces roseofulvus gap 39.572.8 342 glyceraldehyde-3-phosphate dehydrogenase 1045 4545 994474994106 369 GSP: Y75094 Neisseria meningitidis 54.0 61.0 51 polypeptidespredicted to be useful antigens for vaccines and diagnostics 1046 4546995375 994845 531 sp: PTH_ECOLI Escherichia coli K12 pth 38.5 63.2 174peptidyl-tRNA hydrolase 1047 4547 996126 995527 600 pir: B70622Mycobacterium tuberculosis 47.0 65.0 194 50S ribosomal protein L25 H37RvrplY 1048 4548 996402 996830 429 sp: LGUL_SALTY Salmonella typhimuriumD21 28.7 54.6 143 lactoylglutathione lyase gloA 1049 4549 997456 996833624 prf: 2516401BW Bacillus cereus ATCC 10987 38.9 62.5 208 DNAalkylation repair enzyme alkD 1050 4550 998440 997466 975 sp: KPRS_BACCLBacillus subtilis prs 44.0 79.1 316 ribose-phosphate pyrophosphokinase1051 4551 999909 998455 1455 pir: S66080 Bacillus subtilis gcaD 42.071.9 452 UDP-N-acetylglucosamine pyrophosphorylase 1052 4552 10012421000016 1227 1053 4553 1001332 1002864 1533 sp: SUFI_ECOLI Escherichiacoli K12 sufI 30.8 61.7 506 sufI protein precursor 1054 4554 10030131003930 918 sp: NODI_RHIS3 Rhizobium sp. N33 nodI 35.8 64.8 310nodulation ATP-binding protein I 1055 4555 1003953 1004783 831 pir:JN0850 Streptomyces lividans ORF2 30.2 63.2 272 hypothetical membraneprotein 1056 4556 1004829 1006085 1257 sp: UHPB_ECOLI Escherichia coliK12 uhpB 24.6 48.4 459 two-component system sensor histidine kinase 10574557 1006089 1006697 609 prf: 2107255A Streptomyces peucetius dnrN 36.667.3 202 two component transcriptional regulator (luxR family) 1058 45581006937 1006734 204 1059 4559 1006998 1008152 1155 gp: SCF15_7Streptomyces coelicolor A3(2) 31.5 64.5 349 hypothetical membraneprotein SCF15.07 1060 4560 1008622 1010061 1440 pir: S65587 Streptomycesglaucescens strV 28.6 57.0 535 ABC transporter 1061 4561 1008686 1008534153 1062 4562 1010057 1011790 1734 pir: T14180 Mycobacterium smegmatisexiT 44.0 74.0 573 ABC transporter 1063 4563 1013761 1011797 1965 sp:GGT_ECOLI Escherichia coli K12 ggt 32.4 58.6 666gamma-glutamyltranspeptidase precursor 1064 4564 1014016 1014264 2491065 4565 1014861 1014343 519 1066 4566 1014925 1015116 192 1067 45671015652 1016560 909 1068 4568 1015692 1015450 243 GPU: AF164956_23Corynebacterium glutamicum 64.0 72.0 37 transposase protein fragmentTnpNC 1069 4569 1015852 1015145 708 gp: AF121000_8 Corynebacteriumglutamicum 99.6 100.0 236 transposase (IS1628 TnpB) 22243 R-plasmid pAG1tnpB 1070 4570 1016557 1017018 462 1071 4571 1017870 1017274 597 10724572 1018082 1018393 312 1073 4573 1018416 1019066 651 sp: TETC_ECOLIEscherichia coli tetR 23.0 59.6 183 transcriptional regulator (TetR-family) 1074 4574 1019090 1022716 3627 sp: MFD_ECOLI Escherichia colimfd 36.2 65.1 1217 transcription/repair-coupling protein 1075 45751020613 1019390 1224 1076 4576 1021305 1021078 228 GSP: Y75301 Neisseriagonorrhoeae 48.0 69.0 76 Neisserial polypeptides predicted to be usefulantigens for vaccines and diagnostics 1077 4577 1024666 1022699 1968 sp:MDLB_ECOLI Escherichia coli mdlB 31.3 62.7 632 multidrug resistance-likeATP- binding protein, ABC-type transport protein 1078 4578 10263961024666 1731 sp: YC73_MYCTU Mycobacterium tuberculosis 50.2 81.9 574 ABCtransporter H37Rv Rv1273c 1079 4579 1028886 1026505 2382 sp: YLI3_CORGLCorynebacterium glutamicum 100.0 100.0 368 hypothetical membrane proteinATCC 13032 orf3 1080 4580 1031885 1032181 297 1081 4581 1032196 1032780585 sp: YABN_BACSU Bacillus subtilis yabN 33.4 57.4 183 hypotheticalprotein 1082 4582 1033185 1032760 426 1083 4583 1033646 1033269 378 10844584 1033954 1034739 786 pir: A70623 Mycobacterium tuberculosis 46.568.9 241 lpqU protein H37Rv Rv1022 lpqU 1085 4585 1034949 1036223 1275sp: ENO_BACSU Bacillus subtilis eno 64.5 86.0 422 enolase(2-phosphoglycerate dehydratase)(2-phospho-D- glycerate hydro-lyase)1086 4586 1036159 1036016 144 PIR: B72477 Aeropyrum pernix K1 APE245968.0 58.0 41 hypothetical protein 1087 4587 1036316 1036855 540 pir:C70623 Mycobacterium tuberculosis 31.9 55.0 191 hypothetical proteinH37Rv Rv1024 1088 4588 1036900 1037445 546 pir: D70623 Mycobacteriumtuberculosis 59.5 77.8 153 hypothetical protein H37Rv Rv1025 1089 45891037448 1038410 963 sp: GPPA_ECOLI Escherichia coli gppA 25.2 55.0 329guanosine pentaphosphatase or exopolyphosphatase 1090 4590 10374811036498 984 1091 4591 1039650 1038721 930 sp: THD2_ECOLI Escherichiacoli tdcB 30.3 64.7 314 threonine dehydratase 1092 4592 1039783 1039977195 1093 4593 1039996 1040325 330 1094 4594 1040494 1040682 189 pir:B72287 Thermotoga maritima MSB8 46.3 74.1 56 hypothetical protein 10954595 1040925 1041917 993 sp: RHAR_ECOLI Escherichia coli rhaR 24.8 55.8242 transcription activator of L-rhamnose operon 1096 4596 10420271042842 816 pir: F70893 Mycobacterium tuberculosis 57.8 80.1 282hypothetical protein H37Rv Rv1072 1097 4597 1043236 1042850 387 10984598 1043747 1043298 450 gp: SCF55_39 Streptomyces coelicolor A3(2) 30.057.1 140 hypothetical protein SCF55.39 1099 4599 1044295 1043774 522 sp:GREA_ECOLI Escherichia coli greA 35.0 60.1 143 transcription elongationfactor 1100 4600 1044959 1044477 483 pir: G70894 Mycobacteriumtuberculosis 34.3 72.1 140 hypothetical protein H37Rv Rv1081c 1101 46011045158 1046030 873 pir: S44952 Streptomyces lincolnensis lmbE 31.7 56.3300 lincomycin-production 1102 4602 1046073 1046390 318 1103 46031046610 1047707 1098 sp: AROG_CORGL Corynebacterium glutamicum 99.2 99.5367 3-deoxy-D-arabino-heptulosonate-7- aroG phosphate synthase 1104 46041047452 1046820 633 1105 4605 1047827 1048501 675 sp: YARF_CORGLCorynebacterium glutamicum 96.0 97.3 97 hypothetical protein orundecaprenyl CCRC18310 pyrophosphate synthetase 1106 4606 10483561048529 174 SP: YARF_CORGL Corynebacterium glutamicum 100.0 100.0 28hypothetical protein (Brevibacterium flavum) 1107 4607 1048525 1049043519 1108 4608 1049385 1049068 318 1109 4609 1050362 1049427 936 sp:COAA_ECOLI Escherichia coli coaA 53.9 79.9 308 pantothenate kinase 11104610 1050624 1051925 1302 gsp: R97745 Brevibacterium flavum MJ-233 99.5100.0 434 serine hydroxymethyl transferase glyA 1111 4611 10520211053880 1860 sp: PABS_STRGR Streptomyces griseus pabS 47.6 70.1 898p-aminobenzoic acid synthase 1112 4612 1053880 1054602 723 1113 46131054859 1055722 864 1114 4614 1055032 1054640 393 1115 4615 10557831056319 537 gp: A01504_1 Alcaligenes faecalis ptcR 30.3 58.8 165phosphinothricin resistance protin 1116 4616 1057200 1056322 879 sp:YBGK_ECOLI Escherichia coli ybgK 30.3 59.0 300 hypothetical protein 11174617 1057573 1058628 1056 1118 4618 1057868 1057200 669 sp: YBGJ_ECOLIEscherichia coli ybgJ 37.8 57.8 225 hypothetical protein 1119 46191058598 1057843 756 sp: LAMB_EMENI Emericella nidulans lamB 30.8 52.2276 lactam utilization protein 1120 4620 1059214 1058624 591 sp:YCSH_BACSU Bacillus subtilis ycsH 40.6 81.2 165 hypothetical membraneprotein 1121 4621 1059218 1059889 672 1122 4622 1059360 1059962 603 11234623 1060112 1060792 681 sp: YDHC_BACSU Bacillus subtilis ydhC 26.0 63.2204 transcriptional regulator 1124 4624 1060869 1062146 1278 1125 46251063629 1062211 1419 sp: FUMH_RAT Rattus norvegicus (Rat) fumH 52.0 79.4456 fumarate hydratase precursor 1126 4626 1063936 1064424 489 gp:AF048979_1 Rhodococcus erythropolis 32.7 65.4 159 NADH-dependent FMNIGTS8 dszD oxydoreductase 1127 4627 1064738 1064478 261 1128 46281065200 1064754 447 1129 4629 1065867 1065304 564 gp: SCAH10_16Streptomyces coelicolor A3(2) 55.4 81.0 184 reductase StAH10.16 11304630 1066083 1067570 1488 sp: SOXA_RHOSO Rhodococcus sp. IGTS8 soxA 39.167.7 443 dibenzothiophene desulfurization enzyme A 1131 4631 10675701068649 1080 sp: SOXC_RHOSO Rhodococcus sp. IGTS8 soxC 25.8 51.3 372dibenzothiophene desulfurization enzyme C (DBT sulfur dioxygenase) 11324632 1068649 1069845 1197 sp: SOXC_RHOSO Rhodococcus sp. IGTS8 soxC 28.961.6 391 dibenzothiophene desulfurization enzyme C (DBT sulfurdioxygenase) 1133 4633 1069692 1068913 780 1134 4634 1069808 1069119 6901135 4635 1069959 1071134 1176 gp: ECO237695_3 Escherichia coli K12 ssuD45.3 73.1 397 FMNH2-dependent aliphatic sulfonate monooxygenase 11364636 1072441 1071479 963 sp: GLPX_ECOLI Escherichia coli K12 glpX 44.375.7 325 glycerol metabolism 1137 4637 1072676 1073245 570 pir: B70897Mycobacterium tuberculosis 27.5 56.4 211 hypothetical protein H37RvRv1100 1138 4638 1075241 1073340 1902 pir: H70062 Bacillus subtilis ywmD31.3 66.1 227 hypothetical protein 1139 4639 1075357 1075641 285 11404640 1075553 1075329 225 gp: SCH24_37 Streptomyces coelicolor A3(2) 36.678.1 82 transmembrane efflux protein SCH24.37 1141 4641 1075909 1075667243 sp: EX7S_ECOLI Escherichia coli K12 MG1655 40.3 67.7 62exodeoxyribonuclease small subunit xseB 1142 4642 1077183 1075933 1251sp: EX7L_ECOLI Escherichia coli K12 MG1655 30.0 55.6 466exodeoxyribonuclease large subunit xseA 1143 4643 1077297 1078271 975sp: LYTB_ECOLI Escherichia coli K12 lytB 50.2 78.8 311 penicillintolerance 1144 4644 1077734 1077306 429 GSP: Y75421 Neisseriagonorrhoeae 33.0 47.0 131 polypeptides predicted to be useful antigensfor vaccines and diagnostics 1145 4645 1079146 1078319 828 1146 46461080540 1079221 1320 sp: PERM_ECOLI Escherichia coli K12 perM 26.3 63.9338 permease 1147 4647 1080965 1080786 180 1148 4648 1082708 10809721737 sp: NTPR_RAT Rattus norvegicus (Rat) SLC6A7 30.3 61.4 552sodium-dependent proline ntpR transporter 1149 4649 1084183 1082951 1233sp: CSP1_CORGL Corynebacterium glutamicum 29.9 60.0 412 major secretedprotein PS1 protein (Brevibacterium flavum) ATCC precursor 17965 csp11150 4650 1084380 1085462 1083 sp: YYAF_BACSU Bacillus subtilis yyaF70.1 88.6 361 GTP-binding protein 1151 4651 1085791 1086087 297 sp:VAPI_BACNO Dichelobacter nodosus intA 57.3 80.0 75 virulence-associatedprotein 1152 4652 1086096 1086917 822 sp: OTCA_PSEAE Pseudomonasaeruginosa argF 29.6 58.8 301 ornithine carbamoyltransferase 1153 46531087544 1087044 501 sp: YKKB_BACSU Bacillus subtilis 168 ykkB 39.2 69.9143 hypothetical protein 1154 4654 1088293 1087664 630 gp: AF013288_1Mus musculus RDH4 33.8 60.6 198 9-cis retinol dehydrogenase oroxidoreductase 1155 4655 1089740 1088535 1206 sp: YIS1_STRCOStreptomyces coelicolor 42.2 73.0 396 transposase/integrase (IS110)SC3C8.10 1156 4656 1090175 1093216 3042 sp: YEGE_ECOLI Escherichia coliK12 yegE 23.0 52.2 1153 hypothetical membrane protein 1157 4657 10939291094693 765 sp: NODC_RHIME Rhizobium meliloti nodC 22.8 47.1 259N-acetylglucosaminyltransferase 1158 4658 1094693 1094911 219 1159 46591095052 1095384 333 1160 4660 1095677 1095387 291 pir: S43613Corynebacterium glutamicum 82.5 93.8 97 transposase (insertion sequenceATCC 31831 IS31831) 1161 4661 1096093 1095719 375 pir: JC4742Corynebacterium glutamicum 79.2 94.4 125 transposase (Brevibacteriumlactofermentum) ATCC 13869 1162 4662 1096331 1096188 144 pir: JC4742Corynebacterium glutamicum 87.5 95.8 48 transposase (Brevibacteriumlactofermentum) ATCC 13869 1163 4663 1096471 1096331 141 1164 46641097111 1096746 366 1165 4665 1097229 1097726 498 1166 4666 10977501098592 843 sp: MORA_PSEPU Pseudomonas putida M10 norA 37.5 66.3 264oxidoreductase or morpyine-6- dehydrogenase (naloxone reductase) 11674667 1098609 1098929 321 sp: DC4C_ACICA Acinetobacter calcoaceticus 33.363.9 108 4-carboxymuconolactone dc4c decarboxlyase 1168 4668 10990881099750 663 1169 4669 1099209 1099015 195 1170 4670 1099768 1099115 654gp: AF058302_19 Streptomyces roseofulvus frnS 34.9 66.4 146 frenolicingene cluster protein involved in frenolicin biosynthetic 1171 46711099917 1101653 1737 gp: SPU59234_3 Synechococcus sp. PCC 7942 48.1 78.5563 biotin carboxylase accC 1172 4672 1102043 1102639 597 1173 46731102695 1103192 498 1174 4674 1103180 1103524 345 1175 4675 11039511104103 153 1176 4676 1104923 1105561 639 1177 4677 1106058 1104103 1956sp: YT15_MYCTU Mycobacterium tuberculosis 57.9 80.3 655 hypotheticalprotein H37Rv Rv0959 1178 4678 1107381 1106086 1296 sp: BCHI_RHOSHRhodobacter sphaeroides ATCC 27.7 52.6 329 magnesium chelatase subunit17023 bchl 1179 4679 1107560 1108201 642 gp: AMU73808_1 Amycolatopsismethanolica pgm 33.8 62.5 160 2,3-PDG dependent phosphoglycerate mutase1180 4680 1108201 1108905 705 pir: A70577 Mycobacterium tuberculosis38.2 60.7 262 hypothetical protein H37Rv Rv2133c 1181 4681 11089931109754 762 gp: STMBCPA_1 Streptomyces hygroscopicus 29.4 59.3 248carboxyphosphonoenolpyruvate SF1293 BcpA phosphonomutase 1182 46821109792 1111432 1641 sp: TLRC_STRFR Streptomyces fradiae tlrC 31.7 54.1593 tyrosin resistance ATP-binding protein 1183 4683 1111820 1111425 396sp: Y06C_MYCTU Mycobacterium tuberculosis 29.4 66.9 136 hypotheticalprotein H37Rv Rv2923c 1184 4684 1111889 1112230 342 sp: PHNA_ECOLIEscherichia coli K12 MG1655 55.0 82.0 111 alkylphosphonate uptakeprotein phnA 1185 4685 1112957 1112484 474 sp: YXAD_BACSU Bacillussubtilis 168 yxaD 32.1 62.7 134 transcriptional regulator 1186 46861113102 1114319 1218 gp: SPN7367_1 Streptococcus pneumoniae 22.6 59.4367 multi-drug resistance efflux pump pmrA 1187 4687 1114486 11157931308 pir: S43613 Corynebacterium glutamicum 99.5 99.8 436 transposase(insertion sequence (Brevibacterium lactofermentum) IS31831) ATCC 318311188 4688 1116905 1115832 1074 gp: RFAJ3152_2 Ruminococcus flavefaciens43.9 73.4 376 cysteine desulphurase cysteine desulphurase gene 1189 46891117744 1116908 837 sp: NADC_MYCTU Mycobacterium tuberculosis 42.1 68.9283 nicotinate-nucleotide pyrophosphorylase 1190 4690 1118932 11177511182 pir: E69663 Bacillus subtilis nadA 49.3 77.6 361 quinolinatesynthetase A 1191 4691 1119727 1119086 642 gp: SC5B8_7 Streptomycescoelicolor 37.0 60.9 235 DNA hydrolase SC5B8.07 1192 4692 11202051120804 600 gp: AE001961_5 Deinococcus radiodurans R1 23.4 54.7 192hypothetical membrane protein DR1112 1193 4693 1121432 1120833 600 gp:SC3A7_8 Streptomyces coelicolor 36.0 66.4 214 hypothetical proteinSC3A7.08 1194 4694 1121809 1121468 342 sp: YBDF_ECOLI Escherichia coliK12 MG1655 41.7 74.1 108 hypothetical protein ybdF 1195 4695 11226061121818 789 gp: AAA21740_1 Escherichia coli K12 lplA 30.1 60.7 216lipoate-protein ligase A 1196 4696 1123051 1123461 411 sp: PHNB_ECOLIEscherichia coli K12 phnB 29.7 60.8 148 alkylphosphonate uptake proteinand C-P lyase activity 1197 4697 1124826 1123534 1293 sp: PCAK_PSEPUPseudomonas putida pcaK 28.8 64.3 420 transmembrane transport protein or4-hydroxybenzoate transporter 1198 4698 1126020 1124836 1185 sp:PHHY_PSEAE Pseudomonas aeruginosa phhy 40.8 68.6 395 p-hydroxybenzoatehydroxylase (4- hydroxybenzoate 3- monooxygenase) 1199 4699 11264221127009 588 pir: A69859 Bacillus subtilis 168 ykoE 36.7 69.6 191hypothetical membrane protein 1200 4700 1127013 1128350 1338 sp:YJJK_ECOLI Escherichia coli yjjK 24.8 47.6 532 ABC transporterATP-binding protein 1201 4701 1128350 1129102 753 pir: G69858 Bacillussubtilis 168 ykoC 25.6 61.6 250 hypothetical membrane protein 1202 47021129102 1129632 531 1203 4703 1129655 1130704 1050 sp: CHAA_ECOLIEscherichia coli chaA 33.3 69.0 339 Ca2+/H+ antiporter ChaA 1204 47041130721 1131428 708 pir: C75001 Pyrococcus abyssi Orsay 28.4 57.6 236hypothetical protein PAB1341 1205 4705 1132123 1131401 723 sp:YWAF_BACSU Bacillus subtilis ywaF 27.6 61.1 221 hypothetical membraneprotein 1206 4706 1134472 1132133 2340 sp: UVRA_THETH Thermusthermophilus unrA 35.5 58.7 946 excinuclease ABC subunit A 1207 47071134561 1135055 495 sp: TPX_MYCTU Mycobacterium tuberculosis 57.3 81.7164 thioredoxin peroxidase H37Rv tpx 1208 4708 1135476 1135691 216 12094709 1136833 1135058 1776 1210 4710 1137891 1136938 954 sp: YEDI_ECOLIEscherichia coli yedL 39.9 72.0 318 hypothetical membrane protein 12114711 1137960 1138859 900 gp: SCF76_2 Streptomyces coelicolor A3(2) 34.049.0 282 oxidoreductase or thiamin biosynthesis protein 1212 47121138880 1139245 366 1213 4713 1139196 1139492 297 1214 4714 11393571139617 261 1215 4715 1140021 1139635 387 1216 4716 1140861 1140028 834sp: CTR2_PENVA Penaeus vannamei 28.8 51.3 271 chymotrypsin BII 1217 47171141245 1140901 345 sp: ARC2_ECOLI Escherichia coli 43.2 72.1 111arsenate reductase (arsenical pump modifier) 1218 4718 1141273 11424721200 sp: YYAD_BACSU Bacillus subtilis yyaD 23.5 62.4 340 hypotheticalmembrane protein 1219 4719 1143015 1142479 537 pir: F70559 Mycobacteriumtuberculosis 43.5 71.4 147 hypothetical protein H37Rv Rv1632c 1220 47201143739 1143026 714 pir: F70555 Mycobacterium tuberculosis 35.8 62.9 221hypothetical protein H37Rv Rv1157c 1221 4721 1144118 1146028 1911 sp:TYPA_ECOLI Escherichia coli K12 typA 46.3 76.7 614 GTP-binding protein(tyrosine phsphorylated protein A) 1222 4722 1146097 1147602 1506 pir:F70874 Mycobacterium tuberculosis 27.9 54.9 506 hypothetical proteinH37Rv Rv1166 1223 4723 1147592 1148461 870 pir: B70875 Mycobacteriumtuberculosis 38.7 61.9 315 hypothetical protein H37Rv Rv1170 1224 47241148445 1148882 438 1225 4725 1148953 1149267 315 sp: FER_STRGRStreptomyces griseus fer 78.6 91.3 103 ferredoxin [4Fe-4S] 1226 47261149279 1150379 1101 sp: AAT_BACSP Bacillus sp: strain YM-2 aat 25.952.9 397 aspartate aminotransferase 1227 4727 1150408 1151028 621 12284728 1151186 1152370 1185 1229 4729 1153263 1152373 891 gp: CGAJ4934_1Corynebacterium glutamicum 100.0 100.0 229 tetrahydrodipicolinatesuccinylase or ATCC 13032 dapD succinylation of piperidine-2,6-dicarboxylate 1230 4730 1156537 1155875 663 1231 4731 1156902 1157669768 pir: S60064 Corynebacterium glutamicum 100.0 100.0 211 hypotheticalprotein ATCC 13032 orf2 1232 4732 1157694 1158524 831 gp: SCP8_4Streptomyces coelicolor A3(2) 59.0 69.0 273 dihydropteroate synthasedhpS 1233 4733 1158524 1159252 729 gp: MLU15180_14 Mycobacterium lepraeu1756I 45.7 73.1 245 hypothetical protein 1234 4734 1159267 1159572 306pir: G70609 Mycobacterium tuberculosis 31.3 67.7 99 hypothetical proteinH37Rv Rv1209 1235 4735 1159635 1159799 165 gsp: W32443 Mycobacteriumtuberculosis 72.3 91.5 47 antigen TbAAMK, useful in vaccines forprevention or treatment of tuberculosis 1236 4736 1159865 1160728 864sp: MYRA_MICGR Micromonospora griseorubida 39.2 67.8 286mycinamicin-resistance gene myrA 1237 4737 1162231 1160738 1494 sp:SCRB_PEDPE Pediococcus pentosaceus scrB 23.5 51.0 524sucrose-6-phosphate hydrolase 1238 4738 1163605 1162379 1227 sp:GLGA_ECOLI Escherichia coli K12 MG1655 24.7 51.3 433ADPglucose—starch(bacterial glgA glycogen) glucosyltransferase 1239 47391163702 1164916 1215 sp: GLGC_STRCO Streptomyces coelicolor A3(2) 61.081.8 400 glucose-1-phosphate glgC adenylyltransferase 1240 4740 11656121164974 639 sp: MDMC_STRMY Streptomyces mycarofaciens 25.8 62.4 93methyltransferase MdmC 1241 4741 1165746 1166384 639 sp: RPOE_ECOLIEscherichia coli rpoE 27.3 57.2 194 RNA polymerase sigma factor(sigma-24); heat shock and oxidative stress 1242 4742 1166576 1167067492 1243 4743 1167110 1167577 468 pir: C70508 Mycobacterium tuberculosis45.5 73.2 112 hypothetical protein H37Rv Rv1224 1244 4744 11687111167587 1125 sp: MRP_ECOLI Escherichia coli mrp 43.6 72.0 257 ATPase1245 4745 1169325 1168747 579 pir: B70509 Mycobacterium tuberculosis60.4 83.8 154 hypothetical protein H37Rv Rv1231c 1246 4746 11706101169321 1290 pir: C70509 Mycobacterium tuberculosis 49.8 77.0 434hypothetical protein H37Rv Rv1232c 1247 4747 1170672 1171187 516 pir:A70952 Mycobacterium tuberculosis 57.9 87.1 140 hypothetical proteinH37Rv Rv1234 1248 4748 1171206 1171871 666 1249 4749 1172462 1171869 5941250 4750 1176271 1172501 3771 prf: 2306367A Corynebacterium glutamicum99.4 99.8 1257 2-oxoglutarate dehydrogenase AJ12036 odhA 1251 47511180048 1176308 3741 sp: MDR2_CRIGR Cricetulus griseus (Chinese 28.860.4 1288 ABC transporter or multidrug hamster) MDR2 resistance protein2 (P-glycoprotein 2) 1252 4752 1180837 1180121 717 pir: H70953Mycobacterium tuberculosis 31.7 72.1 240 hypothetical protein H37RvRv1249c 1253 4753 1181675 1180872 804 sp: AROE_ECOLI Escherichia coliaroE 25.5 61.2 255 shikimate dehydrogenase 1254 4754 1181993 11836031611 sp: PNBA_BACSU Bacillus subtilis pnbA 35.7 64.7 501para-nitrobenzyl esterase 1255 4755 1183607 1184257 651 1256 47561184280 1185155 876 1257 4757 1185742 1185218 525 1258 4758 11858251187039 1215 sp: TCR1_ECOLI Escherichia coli transposon 27.1 61.4 409tetracycline resistance protein Tn1721 tetA 1259 4759 1187043 11883891347 sp: TCMA_STRGA Streptomyces glaucescens tcmA 32.4 64.2 444metabolite export pump of tetracenomycin C resistance 1260 4760 11898221190526 705 1261 4761 1190622 1188388 2235 pir: S57636 Catharanthusroseus metE 45.2 72.2 774 5- methyltetrahydropteroyltriglutamate—homocysteine S-methyltransferase 1262 4762 1191087 1191542 456 1263 47631192410 1193807 1398 gsp: Y29930 Nocardia asteroides strain KGB1 55.279.5 444 thiophene biotransformation protein 1264 4764 1193867 1194190324 1265 4765 1194165 1195109 945 1266 4766 1195916 1195125 792 12674767 1195974 1197620 1647 1268 4768 1197624 1197815 192 1269 47691199543 1197990 1554 sp: CYDC_ECOLI Escherichia coli K12 MG1655 28.763.5 526 ABC transporter cydC 1270 4770 1201075 1199543 1533 sp:CYDD_ECOLI Escherichia coli K12 MG1655 29.4 58.4 551 ABC transportercydD 1271 4771 1202088 1201090 999 gp: AB035086_2 Corynebacteriumglutamicum 92.0 93.0 333 cytochrome bd-type menaquinol (Brevibacteriumlactofermentum) oxidase subunit II cydB 1272 4772 1203632 1202094 1539gp: AB035086_1 Corynebacterium glutamicum 99.6 99.0 512 cytochromebd-type menaquinol (Brevibacterium lactofermentum) oxidase subunit IcydA 1273 4773 1206180 1203916 2265 sp: YEJH_ECOLI Escherichia coli K12MG1655 26.4 55.0 402 helicase yejH 1274 4774 1206316 1206657 342 12754775 1207223 1206831 393 sp: MUTT_PROVU Proteus vulgaris mutT 36.9 65.698 mutator mutT protein ((7,8-dihydro- 8-oxoguanine-triphosphatase)(8-oxo-dGTPase)(dGTP pyrophosphohydrolase) 1276 4776 1207374 1208138 7651277 4777 1209615 1208212 1404 sp: PROY_SALTY Salmonella typhimuriumproY 51.3 85.0 433 proline-specific permease 1278 4778 1209934 12121292196 sp: DEAD_KLEPN Klebsiella pneumoniae CG43 48.1 74.3 643 DEAD boxATP-dependent RNA DEAD box ATP-dependent RNA helicase helicase deaD 12794779 1213115 1212429 687 prf: 2323363BT Mycobacterium leprae 24.7 47.4247 bacterial regulatory protein, tetR B1308_C2_181 family 1280 47801213269 1214858 1590 sp: PCPB_FLAS3 Sphingomonas flava pcpB 24.5 47.7595 pentachlorophenol 4- monooxygenase 1281 4781 1214871 1215938 1068sp: CLCE_PSESB Pseudomonas sp. B13 clcE 40.4 72.0 354 maleylacetatereductase 1282 4782 1215952 1216836 885 sp: CATA_ACICA Acinetobactercalcoaceticus 30.6 59.4 278 catechol 1,2-dioxygenase catA 1283 47831217374 1216904 471 1284 4784 1217982 1217443 540 pir: A70672Mycobacterium tuberculosis 31.9 58.4 185 hypothetical protein H37RvRv2972c 1285 4785 1219895 1222996 3102 sp: SNF2_YEAST Saccharomycescerevisiae 24.9 55.4 878 transcriptional regulator SNF2 1286 47861222905 1221841 1065 1287 4787 1222986 1223843 858 gp: SCO007731_6Streptomyces coelicolor A3(2) 29.6 56.2 203 hypothetical protein orfZ1288 4788 1223887 1225059 1173 pir: E70755 Mycobacterium tuberculosis39.2 67.3 395 phosphoesterase H37Rv Rv1277 1289 4789 1225066 12276932628 sp: Y084_MYCTU Mycobacterium tuberculosis 29.7 59.6 915hypothetical protein H37Rv Rv1278 1290 4790 1227587 1227282 306 12914791 1227657 1227340 318 1292 4792 1227863 1228636 774 gp: AB029896_1Petroleum-degrading bacterium 37.3 64.6 220 esterase or lipase HD-1 hde1293 4793 1228718 1229095 378 1294 4794 1229150 1229935 786 1295 47951229716 1229180 537 sp: ATOE_ECOLI Streptomyces coelicolor 37.7 69.7 122short-chain fatty acids transporter SC1C2.14c atoE 1296 4796 12299951230480 486 sp: PECS_ERWCH Erwinia chrysanthemi recS 24.7 56.6 166regulatory protein 1297 4797 1230610 1230831 222 1298 4798 12314321230914 519 1299 4799 1231730 1232479 750 sp: FNR_ECOLI Escherichia coliK12 MG1655 fnr 25.0 57.9 228 fumarate (and nitrate) reduction regulatoryprotein 1300 4800 1232603 1232836 234 sp: MERP_SHEPU Shewanellaputrefaciens merP 33.3 66.7 81 mercuric transort protein periplasmiccomponent precursor 1301 4801 1233007 1234881 1875 sp: ATZN_ECOLIEscherichia coli K12 MG1655 38.0 70.6 605 zinc-transporting ATPaseZn(II)- atzN translocating P-type ATPase 1302 4802 1234983 1235612 630sp: RELA_VIBSS Vibrio sp. S14 relA 32.9 58.4 137 GTP pyrophosphokinase(ATP: GTP 3′-pyrophosphotransferase) (ppGpp synthetase I) 1303 48031238125 1236545 1581 gsp: R80504 Streptomyces lividans tap 26.6 49.3 601tripeptidyl aminopeptidase 1304 4804 1242156 1241554 603 1305 48051242275 1242156 120 1306 4806 1243621 1243728 108 GSP: P61449Corynebacterium glutamicum 95.0 98.0 24 homoserine dehydrogenase 13074807 1245201 1243942 1260 1308 4808 1245532 1244843 690 1309 48091246496 1245720 777 sp: NARI_BACSU Bacillus subtilis narI 45.0 69.6 220nitrate reductase gamma chain 1310 4810 1247239 1246508 732 sp:NARJ_BACSU Bacillus subtilis narJ 30.3 63.4 175 nitrate reductase deltachain 1311 4811 1248791 1247199 1593 sp: NARH_BACSU Bacillus subtilisnarH 56.6 83.4 505 nitrate reductase beta chain 1312 4812 12498511250444 594 PIR: D72603 Aeropyrum pernix K1 APE1291 36.0 48.0 137hypothetical protein 1313 4813 1251545 1251817 273 PIR: B72603 Aeropyrumpernix K1 APE1289 36.0 55.0 83 hypothetical protein 1314 4814 12525371248794 3744 sp: NARG_BACSU Bacillus subtilis narG 46.9 73.8 1271nitrate reductase alpha chain 1315 4815 1253906 1252557 1350 sp:NARK_ECOLI Escherichia coli K12 narK 32.8 67.9 461 nitrate extrusionprotein 1316 4816 1254146 1254634 489 sp: CNX1_ARATH Arabidopsisthaliana CV cnx1 32.5 65.0 157 molybdopterin biosynthesis cnx1 protein(molybdenum cofactor biosynthesis enzyme cnx1) 1317 4817 1256602 12547371866 sp: PRTS_SERMA Serratia marcescens strain IFO- 21.1 45.9 738extracellular serine protease 3046 prtS precurosor 1318 4818 12570671257750 684 1319 4819 1257858 1256851 1008 sp: Y0D3_MYCTU Mycobacteriumtuberculosis 30.8 62.6 334 hypothetical membrane protein H37Rv Rv1841c1320 4820 1259265 1257865 1401 sp: Y0D2_MYCTU Mycobacterium tuberculosis31.6 60.2 472 hypothetical membrane protein H37Rv Rv1842c 1321 48211259989 1259429 561 gp: PPU242952_2 Pseudomonas putida mobA 27.5 52.3178 molybdopterin guanine dinucleotide synthase 1322 4822 12612011259993 1209 sp: MOEA_ECOLI Mycobacterium tuberculosis 32.8 58.2 366molybdoptein biosynthesis protein H37Rv Rv0438c moeA 1323 4823 12628181261688 1131 sp: CNX2_ARATH Arabidopsis thaliana cnx2 51.4 73.7 354molybdopterin biosynthsisi protein Moybdenume (mosybdenum cofastorbiosythesis enzyme) 1324 4824 1264610 1262886 1725 sp: ALKK_PSEOLPseudomonas oleovorans 36.7 65.7 572 edium-chain fatty acid—CoA ligase1325 4825 1265142 1267427 2286 sp: RHO_MICLU Micrococcus luteus rho 50.773.8 753 Rho factor 1326 4826 1265665 1266267 603 1327 4827 12663061265611 696 1328 4828 1266449 1265427 1023 1329 4829 1267430 12685031074 sp: RF1_ECOLI Escherichia coli K12 RF-1 41.9 71.9 363 peptide chainrelease factor 1 1330 4830 1268507 1269343 837 sp: HEMK_ECOLIEscherichia coli K12 31.1 57.9 280 protoporphyrinogen oxidase 1331 48311269040 1268267 774 1332 4832 1269396 1270043 648 sp: YD01_MYCTUMycobacterium tuberculosis 62.3 86.0 215 hypothetical protein H37RvRv1301 1333 4833 1270047 1271192 1146 sp: RFE_ECOLI Escherichia coli K12rfe 31.1 58.4 322 undecaprenyl-phosphate alpha-N-acetylglucosaminyltransferase 1334 4834 1271213 1271698 486 1335 48351271871 1272119 249 GPU: AB046112_1 Corynebacterium glutamicum 98.0 99.080 hypothetical protein atpI 1336 4836 1272340 1273149 810 sp:ATP6_ECOLI Escherichia coli K12 atpB 24.1 56.7 245 ATP synthase chain a(protein 6) 1337 4837 1273286 1273525 240 sp: ATPL_STRLI Streptomyceslividans atpL 54.9 85.9 71 H+-transporting ATP synthase lipid- bindingprotein. ATP synthase C chane 1338 4838 1273559 1274122 564 sp:ATPF_STRLI Streptomyces lividans atpF 27.8 66.9 151 H+-transporting ATPsynthase chain b 1339 4839 1274131 1274943 813 sp: ATPD_STRLIStreptomyces lividans atpD 34.3 67.2 274 H+-transporting ATP synthasedelta chain 1340 4840 1274975 1276648 1674 sp: ATPA_STRLI Streptomyceslividans atpA 66.9 88.4 516 H+-transporting ATP synthase alpha chain1341 4841 1276708 1277682 975 sp: ATPG_STRLI Streptomyces lividans atpG46.3 76.6 320 H+-transporting ATP synthase gamma chain 1342 4842 12776881279136 1449 sp: ATPB_CORGL Corynebacterium glutamicum 99.8 100.0 483H+-transporting ATP synthase beta AS019 atpB chain 1343 4843 12791511279522 372 sp: ATPE_STRLI Streptomyces lividans atpE 41.0 73.0 122H+-transporting ATP synthase epsilon chain 1344 4844 1279770 1280240 471sp: Y02W_MYCTU Mycobacterium tuberculosis 38.6 67.4 132 hypotheticalprotein H37Rv Rv1312 1345 4845 1280270 1280959 690 sp: Y036_MYCTUMycobacterium tuberculosis 70.0 85.7 230 hypothetical protein H37RvRv1321 1346 4846 1280967 1281251 285 GP: SC26G5_35 Streptomycescoelicolor A3(2) 45.0 56.0 95 putative ATP/GTP-binding protein 1347 48471281714 1281262 453 sp: YQJC_BACSU Bacillus subtilis yqjC 35.8 68.7 134hypothetical protein 1348 4848 1281794 1282105 312 sp: YC20_MYCTUMycobacterium tuberculosis 54.5 79.2 101 hypothetical protein H37RvRv1898 1349 4849 1282194 1283114 921 sp: YD24_MYCTU Mycobacteriumtuberculosis 37.9 71.4 301 thioredoxin H37Rv Rv1324 1350 4850 12833241284466 1143 gp: ECO237695_3 Escherichia coli K12 ssuD 50.3 74.3 366FMNH2-dependent aliphatic sulfonate monooxygenase 1351 4851 12845171285284 768 sp: SSUC_ECOLI Escherichia coli K12 ssuC 40.8 75.8 240alphatic sulfonates transport permease protein 1352 4852 1285302 1286030729 sp: SSUB_ECOLI Escherichia coli K12 ssuB 50.4 72.8 228 alphaticsulfonates transport permease protein 1353 4853 1286043 1286999 957 sp:SSUA_ECOLI Escherichia coli K12 ssuA 35.1 62.1 311 sulfonate bindingprotein precursor 1354 4854 1289473 1287281 2193 sp: GLGB_ECOLIMycobacterium tuberculosis 46.1 72.7 710 1,4-alpha-glucan branchingenzyme H37Rv Rv1326c glgB (glycogen branching enzyme) 1355 4855 12910071289514 1494 sp: AMY3_DICTH Dictyoglomus thermophilum 22.9 50.5 467alpha-amylase amyC 1356 4856 1291026 1291373 348 1357 4857 12916991292577 879 sp: FEPC_ECOLI Escherichia coli K12 fepC 31.8 87.6 211ferric enterobactin transport ATP- binding protein or ABC transportATP-binding protein 1358 4858 1293222 1294025 804 pir: C70860Mycobacterium tuberculosis 39.6 68.5 260 hypothetical protein H37RvRv3040c 1359 4859 1294151 1295206 1056 pir: H70859 Mycobacteriumtuberculosis 43.1 70.0 367 hypothetical protein H37Rv Rv3037c 1360 48601295047 1294436 612 1361 4861 1295435 1296220 786 sp: FIXA_RHIMERhizobium meliloti fixA 31.2 64.8 244 electron transfer flavoproteinbeta- subunit 1362 4862 1296253 1297203 951 sp: FIXB_RHIME Rhizobiummeliloti fixB 33.1 61.8 335 electron transfer flavoprotein alpha subunitfor various dehydrogenases 1363 4863 1296479 1297093 615 1364 48641297212 1298339 1128 sp: NIFS_AZOVI Azotobacter vinelandii nifS 35.267.7 375 nitrogenase cofactor sythesis protein 1365 4865 1298653 1298342312 1366 4866 1300145 1299000 1146 sp: Y4ME_RHISN Rhizobium sp. NGR234plasmid 29.5 55.7 397 hypothetical protein pNGR234a y4mE 1367 48671300369 1300145 225 sp: Y4MF_RHISN Rhizobium sp. NGR234 plasmid 47.576.3 59 transcriptional regulator pNGR234a Y4mF 1368 4868 13005521301055 504 sp: YHBS_ECOLI Escherichia coli K12 MG1655 34.8 55.3 181acetyltransferase 1369 4869 1301929 1300988 942 1370 4870 13031231301975 1149 1371 4871 1303299 1303694 396 1372 4872 1303829 13049231095 pir: C70858 Mycobacterium tuberculosis 61.8 80.9 361 tRNA(5-methylaminomethyl-2- H37Rv Rv3024c thiouridylate)-methyltransferase1373 4873 1304536 1303883 654 1374 4874 1304932 1305921 990 pir: B70857Mycobacterium tuberculosis 33.7 66.0 332 hypothetical protein H37RvRv3015c 1375 4875 1307384 1305924 1461 sp: TCMA_STRGA Streptomycesglaucescens tcmA 30.2 65.8 500 tetracenomycin C resistance and exportprotin 1376 4876 1308196 1307462 735 1377 4877 1308330 1310369 2040 sp:DNLJ_RHOMR Rhodothermus marinus dnlJ 42.8 70.6 677 DNA ligase(polydeoxyribonucleotide synthase [NAD+] 1378 4878 1311097 1310435 663pir: H70856 Mycobacterium tuberculosis 40.0 70.9 220 hypotheticalprotein H37Rv Rv3013 1379 4879 1311320 1311616 297 sp: GATC_STRCOStreptomyces coelicolor A3(2) 53.0 64.0 97 glutamyl-tRNA(Gln) gatCamidotransferase subunit C 1380 4880 1311625 1313115 1491 sp: GATA_MYCTUMycobacterium tuberculosis 74.0 83.0 484 glutamyl-tRNA(Gln) H37Rv gatAamidotransferase subunit A 1381 4881 1313270 1314118 849 sp: VIUB_VIBVUVibrio vulnificus viuB 28.1 54.0 263 vibriobactin utilizationprotein/iron- chelator utilization protein 1382 4882 1314775 1314470 306gp: SCE6_24 Streptomyces coelicolor A3(2) 46.9 79.2 96 hypotheticalmembrane protein SCE6.24 1383 4883 1315013 1316083 1071 sp: PFP_AMYMEAmycolatopsis methanolica pfp 54.8 77.9 358 pyrophosphate—fructose 6-phosphate 1-phosphotransrefase 1384 4884 1315954 1315325 630 1385 48851316338 1317444 1107 sp: CCPA_BACME Bacillus megaterium ccpA 31.4 31.4328 glucose-resistance amylase regulator (catabolite control protein)1386 4886 1317434 1319005 1572 sp: RBSA_ECOLI Escherichia coli K12 rbsA44.7 76.2 499 ripose transport ATP-binding protein 1387 4887 13190051319976 972 sp: RBSC_ECOLI Escherichia coli K12 MG1655 45.6 76.9 329high affinity ribose transport protein rbsC 1388 4888 1320001 1320942942 sp: RBSB_ECOLI Escherichia coli K12 MG1655 45.9 77.7 305 periplasmicribose-binding protein rbsB 1389 4889 1320952 1321320 369 sp: RBSD_ECOLIEscherichia coli K12 MG1655 41.7 68.4 139 high affinity ribose transportprotein rbsD 1390 4890 1321476 1322111 636 sp: YIW2_YEAST Saccharomycescerevisiae 31.0 58.0 200 hypothetical protein YIR042c 1391 4891 13223931323406 1014 gp: SCF34_13 Streptomyces coelicolor 31.4 60.2 354iron-siderophore binding lipoprotein SCF34.13c 1392 4892 1323533 13245371005 sp: NTCI_RAT Rattus norvegicus (Rat) NTCI 35.8 61.9 268Na-dependent blle acid transporter 1393 4893 1324778 1326256 1479 gsp:W61467 Staphylococcus aureus WHU 29 43.1 71.8 485 RNA-dependentamidotransferase B ratB 1394 4894 1326378 1327049 672 sp: F4RE_METJAMethanococcus jannaschii 32.6 61.1 172 putative F420-dependent NADHMJ1501 f4re reductase 1395 4895 1330967 1329891 1077 sp: YQJG_ECOLIEscherichia coli K12 yqjG 39.8 66.9 317 hypothetical protein 1396 48961331102 1331875 774 pir: A70672 Mycobacterium tuberculosis 39.3 62.4 234hypothetical protein H37Rv Rv2972c 1397 4897 1331953 1333008 1056 pir:H70855 Mycobacterium tuberculosis 27.4 52.6 325 hypothetical membraneprotein H37Rv Rv3005c 1398 4898 1333424 1333188 237 1399 4899 13352801333442 1839 gp: AJ012293_1 Corynebacterium glutamicum 99.2 99.4 613dihydroxy-acid dehydratase ATCC 13032 llvD 1400 4900 1335975 1335412 564pir: G70855 Mycobacterium tuberculosis 33.3 68.6 105 hypotheticalprotein H37Rv Rv3004 1401 4901 1337567 1336095 1473 sp: YILV_CORGLCorynebacterium glutamicum 100.0 100.0 62 hypothetical membrane proteinATCC 13032 yilV 1402 4902 1338609 1338379 231 GP: SSU18930_263Sulfolobus solfataricus 45.0 55.0 66 hypothetical protein 1403 49031342072 1342677 606 1404 4904 1342457 1341960 498 sp: NRTD_SYNP7Synechococcus sp. nrtD 50.9 80.8 167 nitrate transport ATP-bindingpotein 1405 4905 1342727 1342461 267 sp: MALK_ENTAE Enterobacteraerogenes 46.0 78.2 87 maltose/maltodextrin transport ATP- (Aerobacteraerogenes) malK binding protein 1406 4906 1343675 1342794 882 sp:NRTA_ANASP Anabaena sp. strain PCC 7120 28.1 56.8 324 nitratetransporter protein nrtA 1407 4907 1344018 1344464 447 1408 4908 13444401344808 369 1409 4909 1344935 1345420 486 sp: DIM6_STRCO Streptomycescoelicolor 39.4 73.2 142 actinorhodin polyketide dimerase 1410 49101345486 1346439 954 sp: CZCD_ALCEU Ralstonia eutropha czcD 39.1 72.7 304cobalt-zinc-cadimium resistance protein 1411 4911 1345487 1345335 1531412 4912 1346331 1345642 690 1413 4913 1346458 1348272 1815 sp:V686_METJA Methanococcus jannaschii 22.9 53.7 642 hypothetical protein1414 4914 1348334 1350076 1743 1415 4915 1350855 1352444 1590 gsp:Y22646 Brevibacterium flavum serA 99.8 100.0 530 D-3-phosphoglyceratedehydrogenase 1416 4916 1352053 1351727 327 SP: YEN1_SCHPOSchizosaccharomyces pombe 29.0 52.0 105 hypothetical serine-rich proteinSPAC11G7.01 1417 4917 1352585 1353451 867 1418 4918 1355601 1354540 10621419 4919 1355689 1357554 1866 pir: T03476 Rhodobacter capsulatus strain32.9 63.1 620 hypothetical protein SB1003 1420 4920 1356452 1356853 4021421 4921 1357557 1358210 654 1422 4922 1358259 1359062 804 sp:HPCE_ECOLI Escherichia coli C hpcE 33.3 59.2 228 homoprotocatechiuatecatabolism bifunctional isomerase/decarboxylase [includes:2-hydroxyhepta-2,4-diene-1,7-dioate isomerase(hhdd isomerase); 5-carboxymethyl-2-oxo-hex-3-ene-1,7- dioate decarboxylase(opetdecarboxylase)] 1423 4923 1359052 1359669 618 sp: UBIG_ECOLI Escherichiacoli K12 23.4 55.7 192 methyltransferase or 3- demethylubiquinone-9 3-O-methyltransferase 1424 4924 1361295 1360168 1128 sp: DHBC_BACSU Bacillussubtilis dhbC 38.0 70.4 371 isochorismate synthase 1425 4925 13613611362848 1488 sp: SYE_BACSU Bacillus subtilis gltX 37.3 69.7 485glutamyl-tRNA synthetase 1426 4926 1363138 1362926 213 gp: SCJ33_10Streptomyces coelicolor A3(2) 77.0 90.0 67 transcriptional regulator1427 4927 1363657 1363142 516 1428 4928 1364253 1363732 522 1429 49291364915 1365256 342 1430 4930 1364960 1364340 621 1431 4931 13651801364878 303 1432 4932 1365396 1365217 180 1433 4933 1365808 1366137 3301434 4934 1367293 1367505 213 1435 4935 1368070 1367888 183 1436 49361368078 1368395 318 1437 4937 1368400 1369551 1152 1438 4938 13695511369874 324 1439 4939 1371637 1369877 1761 sp: THIC_BACSU Bacillussubtilis thiA or thiC 65.1 81.0 599 thiamin biosynthesis protein 14404940 1372326 1371979 348 1441 4941 1372601 1373131 531 1442 4942 13737981373929 132 GSP: Y37857 Chlamydia trachomatis 61.0 74.0 44 lipoprotein1443 4943 1374556 1375491 936 1444 4944 1375776 1373350 2427 sp:PHS1_RAT Rattus norvegicus (Rat) 44.2 74.0 797 glycogen phosphorylase1445 4945 1375987 1375805 183 1446 4946 1376088 1375933 156 1447 49471377555 1376149 1407 sp: YRKH_BACSU Bacillus subtilis yrkH 25.4 52.8 299hypothetical protein 1448 4948 1378415 1377666 750 sp: Y441_METJAMethanococcus jannaschii Y441 25.4 64.8 256 hypothetical membraneprotein 1449 4949 1378942 1378466 477 1450 4950 1379003 1379566 564 sp:SPOT_ECOLI Escherichia coli K12 spoT 29.8 60.1 178 guanosine3′,5′-bis(diphosphate) 3′- pyrophosphatase 1451 4951 1380259 1379555 705sp: ICLR_ECOLI Escherichia coli K12 iclR 26.1 60.7 257 acetate repressorprotein 1452 4952 1380440 1381882 1443 sp: LEU2_ACTTI Actinoplanesteichomyceticus 68.1 87.5 473 3-isopropylmalate dehydratase large leu2subunit 1453 4953 1381902 1382492 591 sp: LEUD_SALTY Salmonellatyphimurium 67.7 89.2 195 3-isopropylmalate dehydratase small subunit1454 4954 1382819 1382502 318 1455 4955 1383798 1382845 954 gp:MLCB637_35 Mycobacterium tuberculosis 45.9 71.4 294 mutator mutT protein((7,8-dihydro- H37Rv MLCB637.35c 8-oxoguanine-triphosphatase)(8-oxo-dGTPase)(dGTP pyrophosphohydrolase) 1456 4956 1383930 1384085 1561457 4957 1384130 1385125 996 sp: GPDA_BACSU Bacillus subtilis gpdA 45.072.2 331 NAD(P)H-dependent dihydroxyacetone phosphate reductase 14584958 1385153 1386232 1080 sp: DDLA_ECOLI Escherichia coli K12 MG165540.4 67.4 374 D-alanine-D-alanine ligase ddlA 1459 4959 1387270 1386293978 1460 4960 1387332 1388324 993 sp: THIL_ECOLI Escherichia coli K12thiL 32.2 57.6 335 thiamin-phosphate kinase 1461 4961 1388312 1389073762 sp: UNG_MOUSE Mus musculus ung 38.8 59.6 245 uracil-DNA glycosylaseprecursor 1462 4962 1389208 1390788 1581 sp: Y369_MYCGE Mycoplasmagenitalium (SGC3) 23.1 56.3 568 hypothetical protein MG369 1463 49631390796 1392916 2121 sp: RECG_ECOLI Escherichia coli K12 recG 35.4 60.0693 ATP-dependent DNA helicase 1464 4964 1391961 1391638 324 GSP: Y75303Neisseria meningitidis 31.0 48.0 108 polypeptides predicted to be usefulantigens for vaccines and diagnostics 1465 4965 1392939 1393151 213 sp:BCCP_PROFR Propionibacterium freudenreichii 38.8 67.2 67 biotin carboxylcarrier protein subsp. Shermanii 1466 4966 1393154 1393735 582 sp:YHHF_ECOLI Escherichia coli K12 yhhF 37.1 63.5 167 methylase 1467 49671393742 1394221 480 sp: KDTB_ECOLI Escherichia coli K12 MG1655 42.6 78.7155 lipopolysaccharide core biosynthesis kdtB protein 1468 4968 13948541395933 1080 1469 4969 1394894 1395097 204 GSP: Y75358 Neisseriagonorrhoeae 67.0 74.0 65 Neisserial polypeptides predicted to be usefulantigens for vaccines and diagnostics 1470 4970 1395549 1394800 750 sp:GLNQ_BACST Bacillus stearothermophilus 56.4 78.6 252 ABC transporter orglutamine ABC glnQ transporter, ATP-binding protein 1471 4971 13964101395568 843 sp: NOCM_AGRT5 Agrobacterium tumefaciens 32.7 75.0 220nopaline transport protein nocM 1472 4972 1397421 1396561 861 sp:GLNH_ECOLI Escherichia coli K12 MG1655 27.4 59.0 234 glutamine-bindingprotein precursor glnH 1473 4973 1397662 1398468 807 1474 4974 13995341398557 978 pir: H69160 Methanobacterium 28.6 60.3 322 hypotheticalmembrane protein thermoautotrophicum MTH465 1475 4975 1400926 1401333408 1476 4976 1400940 1400185 756 sp: VINT_BPL54 Bacteriophage L54a vinT26.9 52.5 223 phage integrase 1477 4977 1401333 1402076 744 1478 49781402272 1402703 432 1479 4979 1402874 1402368 507 1480 4980 14031281403991 864 1481 4981 1403997 1404215 219 1482 4982 1404885 1404694 192pir: S60890 Corynebacterium glutamicum 88.5 96.2 26 insertion element(IS3 related) orf2 1483 4983 1406174 1405320 855 1484 4984 14071091406999 111 PIR: S60890 Corynebacterium glutamicum 89.0 97.0 37hypothetical protein 1485 4985 1407535 1407167 369 1486 4986 14078731407559 315 1487 4987 1409023 1408703 321 1488 4988 1409802 1409428 3751489 4989 1411011 1410064 948 1490 4990 1411424 1411119 306 1491 49911412000 1411437 564 1492 4992 1412351 1412572 222 1493 4993 14129161412626 291 1494 4994 1413745 1416459 2715 sp: DPO1_MYCTU Mycobacteriumtuberculosis 56.3 80.8 896 DNA polymerase I polA 1495 4995 14178831416462 1422 sp: CMCT_NOCLA Streptomyces lactamdurans 33.8 67.8 456cephamycin export protein cmcT 1496 4996 1417962 1418870 909 gp:SCJ9A_15 Streptomyces coelicolor A3(2) 41.3 65.4 283 DNA-binding proteinSCJ9A.15c 1497 4997 1418876 1419748 873 sp: MORA_PSEPU Pseudomonasputida morA 46.5 76.1 284 morphine-6-dehydrogenase 1498 4998 14200361419878 159 1499 4999 1420724 1420071 654 sp: YAFE_ECOLI Streptomycescoelicolor 31.9 58.3 163 hypothetical protein SCH5.13 yafE 1500 50001421099 1422556 1458 sp: RS1_ECOLI Escherichia coli K12 rpsA 39.5 71.4451 30S ribosomal protein S1 1501 5001 1422571 1421096 1476 1502 50021425279 1425878 600 sp: YACE_BRELA Brevibacterium lactofermentum 80.593.9 195 hypothetical protein ATCC 13869 yacE 1503 5003 1426257 14273541098 1504 5004 1427957 1427376 582 1505 5005 1428049 1427804 246 15065006 1428290 1429246 957 1507 5007 1429159 1428224 936 sp: IUNH_CRIFACrithidia fasciculata iunH 61.9 81.0 310 inosine-uridine preferringnucleoside hypolase (purine nucleosidase) 1508 5008 1430642 1429194 1449sp: QACA_STAAU Staphylococcus aureus 23.6 53.8 517 aniseptic resistanceprotein 1509 5009 1431579 1430659 921 sp: RBSK_ECOLI Escherichia coliK12 rbsK 35.5 67.6 293 ribose kinase 1510 5010 1432612 1431575 1038 sp:ASCG_ECOLI Escherichia coli K12 ascG 30.0 65.6 337 criptic asc operonrepressor, ranscription regulator 1511 5011 1432750 1433547 798 15125012 1434105 1436201 2097 sp: UVRB_STRPN Streptococcus pneumoniae 57.483.3 671 excinuclease ABC subunit B plasmid pSB470 uvrB 1513 50131436335 1436775 441 sp: Y531_METJA Methanococcus jannaschii 33.6 59.2152 hypothetical protein MJ0531 1514 5014 1437249 1436869 381 sp:YTFH_ECOLI Escherichia coli K12 ytfH 38.8 80.2 121 hypothetical protein1515 5015 1437356 1438201 846 sp: YTFG_ECOLI Escherichia coli K12 ytfG53.8 77.1 279 hypothetical protein 1516 5016 1439343 1440026 684 15175017 1440560 1438212 2349 pir: H70040 Bacillus subtilis yvgS 23.2 47.2839 hypothetical protein 1518 5018 1441586 1440675 912 gp: SC9H11_26Streptomyces coelicolor A3(2) 32.7 68.0 150 hypothetical proteinSC9H11.26c 1519 5019 1442392 1441793 600 sp: YCBL_ECOLI Escherichia coliK12 ycbL 30.4 58.4 214 hydrolase 1520 5020 1442487 1445333 2847 sp:UVRA_ECOLI Escherichia coli K12 uvrA 56.2 80.6 952 excinuclease ABCsubunit A 1521 5021 1444115 1443810 306 PIR: JQ0406 Micrococcus luteus40.0 57.0 100 hypothetical protein 1246 (uvrA region) 1522 5022 14453931444944 450 PIR: JQ0406 Micrococcus luteus 31.0 47.0 142 hypotheticalprotein 1246 (uvrA region) 1523 5023 1446158 1446874 717 1524 50241447446 1445323 2124 1525 5025 1447792 1448358 567 sp: IF3_RHOSHRhodobacter sphaeroides infC 52.5 78.2 179 translation initiation factorIF-3 1526 5026 1448390 1448581 192 sp: RL35_MYCFE Mycoplasma fermentans41.7 76.7 60 50S ribosomal protein L35 1527 5027 1448645 1449025 381 sp:RL20_PSESY Pseudomonas syringae pv. 75.0 92.7 117 50S ribosomal proteinL20 syringae 1528 5028 1449940 1449119 822 1529 5029 1450126 1450692 5671530 5030 1450918 1451820 903 sp: UGPA_ECOLI Escherichia coli K12 MG165533.2 71.6 292 sn-glycerol-3-phosphate transport ugpA system permeaseprotein 1531 5031 1451820 1452653 834 sp: UGPE_ECOLI Escherichia coliK12 MG1655 33.3 70.4 270 sn-glycerol-3-phosphate transport upgE systemprotein 1532 5032 1452758 1454071 1314 sp: UGPB_ECOLI Escherichia coliK12 MG1655 26.6 57.6 436 sn-glycerol-3-phosphate transport ugpB systempermease proein 1533 5033 1454115 1455338 1224 sp: UGPC_ECOLIEscherichia coli K12 MG1655 44.0 71.3 393 sn-glycerol-3-phosphatetransport ugpC ATP-binding protein 1534 5034 1454350 1454102 249 PIR:E72756 Aeropyrum pernix K1 APE0042 47.0 56.0 74 hypothetical protein1535 5035 1456066 1455350 717 sp: GLPQ_BACSU Bacillus subtilis glpQ 26.250.0 244 glycerophosphoryl diester phosphodiesterase 1536 5036 14563551456948 594 sp: TRMH_ECOLI Escherichia coli K12 MG1655 34.0 71.2 153tRNA(guanosine-2′-0-)- trmH methlytransferase 1537 5037 1457047 14580661020 sp: SYFA_BACSU Bacillus subtilis 168 syfA phenylalanyl-tRNAsynthetase alpha chain 1538 5038 1458133 1460616 2484 sp: SYFB_ECOLIEscherichia coli K12 MG1655 42.6 71.7 343 phenylalanyl-tRNA synthetasebeta syfB chain 1539 5039 1458966 1458196 771 1540 5040 1461157 1462128972 sp: ESTA_STRSC Streptomyces scabies estA 26.5 55.1 363 esterase 15415041 1462134 1463516 1383 sp: MDMB_STRMY Streptomyces mycarofaciens 30.056.3 423 macrolide 3-O-acyltransferase mdmB 1542 5042 1463533 1463934402 1543 5043 1464083 1465123 1041 gp: AF005242_1 Corynebacteriumglutamicum 98.3 99.1 347 N-acetylglutamate-5-semialdehyde ASO19 argCdehydrogenase 1544 5044 1465210 1466373 1164 sp: ARGJ_CORGLCorynebacterium glutamicum 99.5 99.7 388 glutamate N-acetyltransferaseATCC 13032 argJ 1545 5045 1467376 1468548 1173 sp: ARGD_CORGLCorynebacterium glutamicum 99.0 99.2 391 acetylornithineaminotransferase ATCC 13032 argD 1546 5046 1470211 1471413 1203 sp:ASSY_CORGL Corynebacterium glutamicum 99.5 99.5 401 argininosuccinatesynthetase ASO19 argG 1547 5047 1471362 1470154 1209 1548 5048 14714771472907 1431 gp: AF048764_1 Corynebacterium glutamicum 83.3 90.0 478argininosuccinate lyase ASO19 argH 1549 5049 1472977 1474119 1143 15505050 1474119 1475693 1575 1551 5051 1475683 1476294 612 1552 50521476343 1476519 177 sp: YCAR_ECOLI Escherichia coli K12 ycaR 48.0 72.050 hypothetical protein 1553 5053 1476550 1477809 1260 sp: SYY1_BACSUBacillus subtilis syy1 48.4 79.6 417 tyrosyl-tRNA synthase (tyrosine—tRNA ligase) 1554 5054 1478393 1477929 465 sp: Y531_METJA Methanococcusjannaschii 26.9 64.4 149 hypothetical protein MJ0531 1555 5055 14788921478503 390 1556 5056 1483475 1483335 141 PIR: F81737 Chlamydiamuridarum Nigg 71.0 75.0 42 hypothetical protein TC0129 1557 50571483996 1483724 273 GSP: Y35814 Chlamydia pneumoniae 61.0 66.0 84hypothetical protein 1558 5058 1484675 1486027 1353 sp: IF2_BORBUBorrelia burgdorferi IF2 36.3 67.0 182 translation initiation factorIF-2 1559 5059 1486042 1487025 984 sp: YZGD_BACSU Bacillus subtilis yzgD29.6 60.1 311 hypothetical protein 1560 5060 1487032 1487193 162 15615061 1487238 1488056 819 sp: YQXC_BACSU Bacillus subtilis yqxC 38.5 69.6260 hypothetical protein 1562 5062 1488146 1489018 873 sp: YFJB_HAEINMycobacterium tuberculosis 31.6 31.6 225 hypothetical protein H37RvRv1695 1563 5063 1489103 1490881 1779 sp: RECN_ECOLI Escherichia coliK12 recN 31.4 63.4 574 DNA repair protein 1564 5064 1490944 1492134 1191pir: H70502 Mycobacterium tuberculosis 41.9 73.1 394 hypotheticalprotein H37Rv Rv1697 1565 5065 1492147 1493109 963 pir: A70503Mycobacterium tuberculosis 30.4 68.1 313 hypothetical protein H37RvRv1698 1566 5066 1493513 1495174 1662 sp: PYRG_ECOLI Escherichia coliK12 pyrG 55.0 76.7 549 CTP synthase (UTP—ammonia ligase) 1567 50671495205 1495861 657 sp: YQKG_BACSU Bacillus subtilis yqkG 36.3 71.3 157hypothetical protein 1568 5068 1495861 1496772 912 gp: AF093548_1Staphylococcus aureus xerD 39.7 71.7 300 tyrosine recombinase 1569 50691498324 1496795 1530 sp: TLRC_STRFR Streptomyces fradiae tlrC 30.5 59.7551 tyrosin resistance ATP-binding protein 1570 5070 1498863 1499645 783gp: CCU87804_4 Caulobacter crescentus parA 44.6 73.6 258 chromosomepartitioning protein or ATPase involved in active partitioning ofdiverse bacterial plasmids 1571 5071 1499931 1500695 765 sp: YPUG_BACSUBacillus subtilis ypuG 28.3 64.5 251 hypothetical protein 1572 50721501471 1500911 561 1573 5073 1501710 1502576 867 gp: AF109156_1 Datiscaglomerata tst 35.6 67.0 270 thiosulfate sulfurtransferase 1574 50741502634 1503176 543 sp: YPUH_BACSU Bacillus subtilis ypuH 33.1 65.7 172hypothetical protein 1575 5075 1503483 1504238 756 sp: RLUB_BACSUBacillus subtilis rluB 45.9 72.5 229 ribosomal large subunitpseudouridine synthase B 1576 5076 1504256 1504945 690 sp: KCY_BACSUBacillus subtilis cmk 38.6 73.6 220 cytidylate kinase 1577 5077 15050171506573 1557 sp: YPHC_BACSU Bacillus subtilis yphC 42.8 74.0 435 GTPbinding protein 1578 5078 1507327 1506662 666 1579 5079 1507902 1507405498 1580 5080 1508729 1507917 813 sp: YX42_MYCTU Mycobacteriumtuberculosis 36.2 67.2 232 methyltransferase Rv3342 1581 5081 15088131510366 1554 prf: 2513302B Corynebacterium striatum M82B 29.7 60.1 499ABC transporter tetA 1582 5082 1510366 1512132 1767 prf: 2513302ACorynebacterium striatum M82B 31.2 56.3 602 ABC transporter tetB 15835083 1511667 1510843 825 1584 5084 1512189 1512977 789 sp: YGIE_ECOLIEscherichia coli K12 ygiE 39.7 73.2 257 hypothetical membrane protein1585 5085 1514505 1514693 189 1586 5086 1514527 1512980 1548 gp:AB029555_1 Bacillus subtilis ATCC 9372 25.7 61.5 499 Na+/H+ antiporternhaG 1587 5087 1515159 1514974 186 1588 5088 1515396 1515815 420 15895089 1515782 1515408 375 sp: YCHJ_ECOLI Escherichia coli K12 o249#9 36.957.7 130 hypothetical protein ychJ 1590 5090 1516962 1515799 1164 pir:C69334 Archaeoglobus fulgidus AF0675 25.2 63.8 2102-hydroxy-6-oxohepta-2,4-dienoate hydrolase 1591 5091 1517170 15194582289 sp: SECA_BACSU Bacillus subtills secA 35.2 61.7 805 preproteintranslocase SecA subunit 1592 5092 1519601 1520029 429 gp: AF173844_2Mycobacterium smegmatis garA 75.8 93.2 132 signal transduction protein1593 5093 1520190 1520945 756 sp: Y0DF_MYCTU Mycobacterium tuberculosis41.9 74.4 234 hypothetical protein H37Rv Rv1828 1594 5094 15209571521589 633 sp: Y0DE_MYCTU Mycobacterium tuberculosis 30.8 63.2 133hypothetical protein H37Rv Rv1828 1595 5095 1521771 1522343 573 sp:Y0DE_MYCTU Mycobacterium tuberculosis 71.4 84.3 178 hypothetical proteinH37Rv Rv1828 1596 5096 1522941 1522432 510 1597 5097 1524500 15230521449 1598 5098 1525374 1525973 600 1599 5099 1525497 1524568 930 16005100 1526534 1525473 1062 sp: YHDP_BACSU Bacillus subtilis yhdP 33.969.0 342 hemolysin 1601 5101 1527913 1526534 1380 sp: YHDT_BACSUBacillus subtilis yhdT 31.4 65.5 65 hemolysin 1602 5102 1527968 1528186219 1603 5103 1529330 1527987 1344 gp: TTHERAGEN_1 Thermus thermophilusherA 41.2 69.5 374 DEAD box RNA helicase 1604 5104 1529486 1530220 735sp: YD48_MYCTU Mycobacterium tuberculosis 34.3 66.1 245 ABC transporterATP-binding protein H37Rv Rv1348 1605 5105 1531816 1530341 1476 gsp:W27613 Brevibacterium flavum 99.0 99.2 492 6-phosphogluconatedehydrogenase 1606 5106 1531933 1532394 462 pir: G70664 Mycobacteriumtuberculosis 39.7 67.8 121 thioesterase H37Rv Rv1847 1607 5107 15323221532996 675 1608 5108 1533041 1533781 741 sp: NODI_RHIS3 Rhizobium sp.N33 nodl 39.6 68.1 235 nodulation ATP-binding protein I 1609 51091533781 1534521 741 pir: E70501 Mycobacterium tuberculosis 43.1 76.3 232hypothetical membrane protein H37Rv Rv1686c 1610 5110 1535401 1534529873 sp: YFHH_ECOLI Escherichia coli K12 yfhH 26.7 63.9 277transcriptional regulator 1611 5111 1536227 1535382 846 sp: PHNE_ECOLIEscherichia coli K12 phnE 29.9 63.4 281 phosphonates transport systempermease protein 1612 5112 1537030 1536227 804 sp: PHNE_ECOLIEscherichia coli K12 phnE 27.2 62.3 268 phosphonates transport systempermease protein 1613 5113 1537833 1537030 804 sp: PHNC_ECOLIEscherichia coli K12 phnC 44.8 72.0 250 phosphonates transportATP-binding protein 1614 5114 1538759 1538968 210 1615 5115 15389191537870 1050 1616 5116 1539664 1538963 702 1617 5117 1541403 15398201584 sp: THID_SALTY Salmonella typhimurium thiD 47.3 70.2 262phosphomethylpyrimidine kinase 1618 5118 1542922 1542119 804 sp:THIM_SALTY Salmonella typhimurium LT2 46.6 77.5 249 hydoxyethylthiazolekinase thiM 1619 5119 1544976 1546289 1314 pir: H70830 Mycobacteriumtuberculosis 28.6 55.0 451 cyclopropane-fatty-acyl-phospholipid H37RvufaA1 synthase 1620 5120 1547692 1546307 1386 prf: 2223339B Burkholderiacepacia Pc701 32.5 66.9 468 sugar transporter or 4-methyl-o- mopBphthalate/phthalate permease 1621 5121 1548440 1547967 474 prf: 2120352BThermus flavus AT-62 gpt 36.5 59.0 156 purine phosphoribosyltransferase1622 5122 1548651 1549349 699 sp: YEBN_ECOLI Escherichia coli K12 yebN39.8 68.5 206 hypothetical protein 1623 5123 1549403 1550398 996 gp:AF178758_2 Sinorhizobium sp. As4 arsB 23.3 54.6 361 arsenicoxyanion-translocation pump membrane subunit 1624 5124 1550469 1550951483 1625 5125 1551545 1552237 693 gp: SCI7_33 Streptomyces coelicolorA3(2) 62.2 83.8 222 hypothetical protein SCI7.33 1626 5126 15525181553972 1455 gp: PSTRTETC1_6 Pseudomonas sp. R9 ORFA 51.8 83.6 469sulfate permease 1627 5127 1553722 1553297 426 GP: PSTRTETC1_7Pseudomonas sp. R9 ORFG 39.0 50.0 97 hypothetical protein 1628 51281554684 1554070 615 1629 5129 1554861 1555067 207 1630 5130 15550791554891 189 1631 5131 1555835 1555086 750 1632 5132 1556376 1556771 396pir: A70945 Mycobacterium tuberculosis 71.8 87.3 110 hypotheticalprotein H37Rv Rv2050 1633 5133 1557823 1557014 810 prf: 2317468ASchizosaccharomyces pombe 39.2 71.0 217 dolichol phosphate mannose dpm1synthase 1634 5134 1559493 1557859 1635 sp: LNT_ECOLI Escherichia coliK12 Int 25.1 55.6 527 apolipoprotein N-acyltransferase 1635 5135 15602371559497 741 1636 5136 1561660 1560437 1224 gp: AF188894_1 Candidaalbicans lip1 23.7 55.6 392 secretory lipase 1637 5137 1561780 1562553774 pir: C70764 Mycobacterium tuberculosis 31.3 56.7 291 precorrin 2methyltransferase H37Rv cobG 1638 5138 1563802 1562525 1278 sp:COBL_PSEDE Pseudomonas denitrificans 32.4 60.8 411 precorrin-6Y C5, 15-SC510 cobL methyltransferase 1639 5139 1563872 1564237 366 1640 51401564237 1564482 246 1641 5141 1565302 1564565 738 sp: YY12_MYCTUMycobacterium tuberculosis 54.1 75.4 244 oxidoreductase H37Rv RV34121642 5142 1566438 1565302 1137 gp: AF014460_1 Streptococcus mutans LT1136.1 61.3 382 dipeptidase or X-Pro dipeptidase pepQ 1643 5143 15664681567106 639 1644 5144 1569903 1567117 2787 sp: MTR4_YEAST Saccharomycescerevisiae 26.5 55.7 1030 ATP-dependent RNA helicase YJL050W dob1 16455145 1570933 1569932 1002 sp: TATC_ECOLI Escherichia coli K12 tatC 28.762.7 268 sec-independent protein translocase protein 1646 5146 15713821571068 315 sp: YY34_MYCLE Mycobacterium leprae 44.7 69.4 85hypothetical protein MLCB2533.27 1647 5147 1572486 1571506 981 sp:YY35_MYCTU Mycobacterium tuberculosis 31.9 61.2 317 hypothetical proteinH37Rv Rv2095c 1648 5148 1573463 1572492 972 sp: YY36_MYCLE Mycobacteriumleprae 32.4 64.8 324 hypothetical protein MLCB2533.25 1649 5149 15749151573491 1425 sp: YY37_MYCTU Mycobacterium tuberculosis 53.1 77.3 467hypothetical protein H37Rv Rv2097c 1650 5150 1574957 1575205 249 16515151 1575136 1574945 192 pir: B70512 Mycobacterium tuberculosis 54.180.3 61 hypothetical protein H37Rv Rv2111c 1652 5152 1576947 15754061542 pir: C70512 Mycobacterium tuberculosis 48.6 74.2 516 hypotheticalprotein H37Rv Rv2112c 1653 5153 1577327 1577806 480 PIR: H72504Aeropyrum pernix K1 APE2014 42.0 50.0 159 hypothetical protein 1654 51541578531 1576951 1581 prf: 2422382Q Rhodococcus erythropolis arc 51.678.5 545 AAA family ATPase (chaperone-like function) 1655 5155 15794001578567 834 pir: S72844 Mycobacterium leprae pimT 57.3 79.0 281protein-beta-aspartate methyltransferase 1656 5156 1580771 1579449 1323gp: AF005050_1 Homo sapiens 38.1 67.2 436 aspartyl aminopeptidase 16575157 1580807 1581640 834 pir: B70513 Mycobacterium tuberculosis 45.471.4 269 hypothetical protein H37Rv Rv2119 1658 5158 1581851 1582114 264sp: VAPI_BACNO Dichelobacter nodosus A198 40.6 72.5 69virulence-associated protein vapI 1659 5159 1583481 1582273 1209 prf:2513299A Staphylococcus aureus norA23 21.8 61.0 385 quinolon resistanceprotein 1660 5160 1585490 1583913 1578 sp: ASPA_CORGL Corynebacteriumglutamicum 99.8 99.8 526 aspartate ammonia-lyase (Brevibacterium flavum)MJ233 aspA 1661 5161 1586445 1585603 843 gp: AF050166_1 Corynebacteriumglutamicum 96.8 97.5 281 ATP phosphoribosyltransferase ASO19 hisG 16625162 1587504 1586812 693 pir: H72277 Thermotoga maritima MSB8 30.8 63.1195 beta-phosphoglucomutase TM1254 1663 5163 1591235 1587573 3663 sp:METH_ECOLI Escherichia coli K12 metH 31.6 62.4 12545-methyltetrahydrofolate— homocysteine methyltransferase 1664 51641591343 1591912 570 1665 5165 1592966 1591941 1026 sp: AHPF_XANCHXanthomonas campestris ahpF 22.4 49.5 366 alkyl hydroperoxide reductasesubunit F 1666 5166 1593337 1594512 1176 sp: ACR3_YEAST Saccharomycescerevisiae 33.0 63.9 388 arsenical-resistance protein S288C YPR201W acr31667 5167 1594532 1594951 420 sp: ARSC_STAAU Staphylococcus aureusplasmid 32.6 64.3 129 arsenate reductase pl258 arsC 1668 5168 15950301595668 639 pir: G70964 Mycobacterium tuberculosis 47.2 75.6 123arsenate reductase H37Rv arsC 1669 5169 1596221 1595844 378 1670 51701597460 1596249 1212 sp: SYC_ECOLI Escherichia coli K12 cysS 35.9 64.3387 cysteinyl-tRNA synthetase 1671 5171 1598623 1597745 879 sp:BACA_ECOLI Escherichia coil K12 bacA 37.3 69.4 255 bacitracin resistanceprotein 1672 5172 1598667 1599614 948 prf: 2214302F Agrobacteriumtumefaciens 33.4 62.6 326 oxidoreductase mocA 1673 5173 1599679 1600677999 pir: F70577 Mycobacterium tuberculosis 27.0 53.5 359 lipoproteinH37Rv lppL 1674 5174 1600692 1601804 1113 sp: PYRD_AGRAE Agrocybeaegerita ura1 44.0 67.1 334 dihydroorotate dehydrogenase 1675 51751602281 1601931 351 1676 5176 1602660 1603466 807 1677 5177 16035201604629 1110 gp: PSESTBCBAD_1 Pseudomonas syringae tnpA 34.7 55.3 360transposase 1678 5178 1605315 1604830 486 1679 5179 1605811 1605281 531sp: YBHB_ECOLI Escherichia coli K12 ybhB 44.1 75.0 152 bio operon ORF I(biotin biosynthetic enzyme) 1680 5180 1605961 1606689 729 GSP: Y74829Neisseria meningitidis 26.0 33.0 198 Neisserial polypeptides predictedto be useful antigens for vaccines and diagnostics 1681 5181 16076461608248 603 1682 5182 1607657 1605861 1797 prf: 2513302A Corynebacteriumstriatum M82B 43.6 68.7 597 ABC transporter tetB 1683 5183 16090871609335 249 1684 5184 1609247 1607661 1587 prf: 2513302B Corynebacteriumstriatum M82B 36.8 67.1 535 ABC transporter tetA 1685 5185 16101921609842 351 1686 5186 1610236 1610844 609 pir: JU0052 Streptomycesanulatus pac 32.4 56.4 56 puromycin N-acetyltransferase 1687 51871612238 1611150 1089 sp: ARGK_ECOLI Escherichia coli K12 argK 43.1 72.3339 LAO(lysine, arginine, and ornithine)/AO (arginine andornithine)transport system kinase 1688 5188 1614444 1612234 2211 sp:MUTB_STRCM Streptomyces cinnamonensis 72.2 87.5 741 methylmalonyl-CoAmutase alpha A3823.5 mutB subunit 1689 5189 1616298 1614451 1848 sp:MUTA_STRCM Streptomyces cinnamonensis 41.6 68.2 610 methylmalonyl-CoAmutase beta A3823.5 mutA subunit 1690 5190 1616578 1617300 723 sp:YS13_MYCTU Mycobacterium tuberculosis 39.7 70.1 224 hypotheticalmembrane protein H37Rv Rv1491c 1691 5191 1617398 1617994 597 1692 51921619616 1618321 1296 sp: YS09_MYCTU Mycobacterium tuberculosis 64.1 87.0370 hypothetical membrane protein H37Rv Rv1488 1693 5193 1620106 1619672435 pir: B70711 Mycobacterium tuberculosis 44.7 78.7 141 hypotheticalmembrane protein H37Rv Rv1487 1694 5194 1621009 1620167 843 gp: SCC77_24Streptomyces coelicolor A3(2) 51.0 72.8 261 hypothetical proteinSCC77.24 1695 5195 1621056 1621838 783 1696 5196 1622950 1621841 1110sp: HEMZ_PROFR Propionibacterium freudenreichii 36.8 65.7 364ferrochelatase subsp. Shermanii hemH 1697 5197 1624826 1623027 1800 sp:P54_ENTFC Streptococcus faecium 25.5 56.5 611 invasin 1698 5198 16259251625428 498 1699 5199 1626279 1629107 2829 pir: F70873 Mycobacteriumtuberculosis 69.9 85.9 959 aconitate hydratase H37Rv acn 1700 52001629298 1629861 564 pir: E70873 Mycobacterium tuberculosis 54.6 81.6 174transcriptional regulator H37Rv Rv1474c 1701 5201 1629913 1630668 756pir: F64496 Methanococcus jannaschii 21.3 51.9 235 GMP synthetase MJ1575guaA 1702 5202 1631329 1630667 663 gp: SCD82_4 Streptomyces coelicolorA3(2) 32.6 62.0 221 hypothetical protein SCD82.04c 1703 5203 16316601631926 267 pir: E64494 Methanococcus jannaschii 37.2 80.2 86hypothetical protein MJ1558 1704 5204 1631745 1631353 393 1705 52051631933 1633324 1392 gp: AE002515_9 Neisseria meningitidis MC58 61.286.1 446 hypothetical protein NMB1652 1706 5206 1632588 1632109 480 GSP:Y38838 Neisseria gonorrhoeae ORF24 54.0 60.0 113 antigenic protein 17075207 1633137 1632682 456 GSP: Y38838 Neisseria gonorrhoeae 59.0 69.0 152antigenic protein 1708 5208 1633566 1636241 2676 sp: ATA1_SYNY3Synechocystis sp. PCC6803 42.6 73.2 883 cation-transporting ATPase Psll1614 pma1 1709 5209 1634563 1633781 783 1710 5210 1636732 1636244 489gp: SC3D11_2 Streptomyces coelicolor A3(2) 35.8 58.3 120 hypotheticalprotein SC3D11.02c 1711 5211 1637081 1638442 1362 1712 5212 16391321638776 357 1713 5213 1639365 1639520 156 1714 5214 1639656 1639817 1621715 5215 1639781 1640155 375 prf: 2408488H Streptococcus thermophilus43.0 73.8 107 host cell surface-exposed lipoprotein phage TP-J34 17165216 1640546 1641001 456 prf: 2510491A Corynephage 304L int 34.4 60.4154 integrase 1717 5217 1642674 1641046 1629 sp: YJJK_ECOLI Escherichiacoli K12 yjjK 32.8 64.4 497 ABC transporter ATP-binding protein 17185218 1644218 1642743 1476 1719 5219 1645499 1644318 1182 sp: NANH_MICVIMicromonospora viridifaciens 51.9 72.4 387 sialidase ATCC 31146 nedA1720 5220 1645661 1646368 708 gp: AF121000_8 Corynebacterium glutamicum99.6 100.0 236 transposase (IS1628) 22243 R-plasmid pAG1 tnpB 1721 52211645821 1646063 243 GPU: AF164956_23 Corynebacterium glutamicum 64.072.0 37 transposase protein fragment TnpNC 1722 5222 1645861 1645601 261GP: NT1TNIS_5 Plasmid NTP16 32.0 43.0 88 hypothetical protein 1723 52231646549 1647133 585 1724 5224 1647634 1647212 423 pir: B75015 Pyrococcusabyssi Orsay 32.7 70.1 107 dTDP-4-keto-L-rhamnose reductase PAB1087 17255225 1648097 1647651 447 pir: S72754 Mycobacterium leprae 63.8 85.2 149nitrogen fixation protein MLCL536.24c nifU7 1726 5226 1648548 1648709162 PIR: C72506 Aeropyrum pernix K1 APE2025 48.0 57.0 52 hypotheticalprotein 1727 5227 1649362 1648100 1263 pir: S72761 Mycobacterium lepraenifS 64.7 84.4 411 nitrogen fixation protein 1728 5228 1650122 1649367756 gp: SCC22_4 Streptomyces coelicolor A3(2) 70.2 89.3 252 ABCtransporter ATP-binding protein SCC22.04c 1729 5229 1651424 1650249 1176pir: A70872 Mycobacterium tuberculosis 55.2 83.0 377 hypotheticalprotein H37Rv Rv1462 1730 5230 1652875 1651433 1443 sp: Y074_SYNY3Synechocystis sp. PCC6803 41.0 73.0 493 ABC transporter slr0074 17315231 1653586 1652894 693 gp: SCC22_8 Streptomyces coelicolor A3(2) 46.171.4 217 DNA-binding protein SCC22.08c 1732 5232 1654043 1655671 1629pir: F70871 Mycobacterium tuberculosis 36.3 67.8 518 hypotheticalmembrane protein H37Rv Rv1459c 1733 5233 1655681 1656700 1020 pir:S72783 Mycobacterium leprae 50.2 77.3 317 ABC transporter MLCL536.31abc2 1734 5234 1656712 1657515 804 pir: S72778 Mycobacterium leprae 41.074.8 266 hypothetical protein MLCL536.32 1735 5235 1657677 1658675 999pir: C70871 Mycobacterium tuberculosis 43.0 74.6 291 hypotheticalprotein H37Rv Rv1456c 1736 5236 1659496 1659140 357 1737 5237 16595081661136 1629 pir: C71156 Pyrococcus horikoshii PH0450 23.4 51.0 418helicase 1738 5238 1661578 1662552 975 sp: QOR_ECOLI Escherichia coliK12 qor 37.5 70.9 323 quinone oxidoreductase 1739 5239 1663598 1662630969 gp: NWCOXABC_3 Nitrobacter winogradskyi coxC 37.6 66.8 295cytochrome o ubiquinol oxidase assembly factor/heme O synthase 1740 52401664403 1666502 2100 gp: AB023377_1 Corynebacterium glutamicum 100.0100.0 675 transketolase ATCC 31833 tkt 1741 5241 1666673 1667752 1080sp: TAL_MYCLE Mycobacterium leprae 62.0 85.2 358 transaldolaseMLCL536.39 tal 1742 5242 1667764 1666601 1164 1743 5243 1667950 16694011452 gsp: W27612 Brevibacterium flavum 99.8 100.0 484glucose-6-phosphate dehydrogenase 1744 5244 1669419 1670375 957 pir:A70917 Mycobacterium tuberculosis 40.6 71.7 318 oxppcycle protein(glucose 6- H37Rv Rv1446c opcA phosphate dehydrogenase assembly protein)1745 5245 1670395 1671099 705 sp: SOL3_YEAST Saccharomyces cerevisiae28.7 58.1 258 6-phosphogluconolactonase S288C YHR163W sol3 1746 52461671677 1671273 405 sp: SAOX_BACSN Bacillus sp. NS-129 35.2 57.8 128sarcosine oxidase 1747 5247 1671723 1673123 1401 gp: AF126281_1Rhodococcus erythropolis 24.6 46.6 500 transposase (IS1676) 1748 52481674105 1673266 840 gp: CGL007732_5 Corynebacterium glutamicum 100.0100.0 205 sarcosine oxidase ATCC 13032 soxA 1749 5249 1677211 1677384174 1750 5250 1678756 1678070 687 1751 5251 1679148 1680128 981 17525252 1681108 1680332 777 sp: TPIS_CORGL Corynebacterium glutamicum 99.299.6 259 triose-phosphate isomerase AS019 ATCC 13059 tpiA 1753 52531681263 1681670 408 SP: YCQ3_YEAST Saccharomyces cerevisiae 37.0 51.0128 probable membrane protein YCR013c 1754 5254 1682404 1681190 1215 sp:PGK_CORGL Corynebacterium glutamicum 98.0 98.5 405 phosphoglyceratekinase AS019 ATCC 13059 pgk 1755 5255 1683625 1682624 1002 sp: G3P_CORGLCorynebacterium glutamicum 99.1 99.7 333 glyceraldehyde-3-phosphateAS019 ATCC 13059 gap dehydrogenase 1756 5256 1685097 1684117 981 pir:D70903 Mycobacterium tuberculosis 63.9 87.4 324 hypothetical proteinH37Rv Rv1423 1757 5257 1686132 1685110 1023 sp: YR40_MYCTU Mycobacteriumtuberculosis 56.3 82.5 309 hypothetical protein H37Rv Rv1422 1758 52581687078 1686152 927 sp: YR39_MYCTU Mycobacterium tuberculosis 52.0 76.2281 hypothetical protein H37Rv Rv1421 1759 5259 1689190 1687103 2088 sp:UVRC_PSEFL Synechocystis sp. PCC6803 34.4 61.5 701 excinuclease ABCsubunit C uvrC 1760 5260 1689779 1689201 579 sp: YR35_MYCTUMycobacterium tuberculosis 32.7 68.7 150 hypothetical protein H37RvRv1417 1761 5261 1690345 1689869 477 SP: RISB_ECOLI Escherichia coli K1243.5 72.1 154 6,7-dimethyl-8-ribityllumazine synthase 1762 5262 16906941690921 228 GSP: Y83273 Bacillus subtilis 59.0 68.0 72 polypeptideencoded by rib operon 1763 5263 1690708 1691421 714 GSP: Y83272 Bacillussubtilis 26.0 48.0 217 riboflavin biosynthetic protein 1764 5264 16910121691347 336 GSP: Y83273 Bacillus subtilis 44.0 52.0 106 polypeptideencoded by rib operon 1765 5265 1691625 1690360 1266 gp: AF001929_1Mycobacterium tuberculosis ribA 65.6 84.7 404 GTP cyclohydrolase II and3,4- dihydroxy-2-butanone 4-phosphate synthase (riboflavin synthesis)1766 5266 1692271 1691639 633 sp: RISA_ACTPL Actinobacillus 47.4 79.2211 riboflavin synthase alpha chain pleuropneumoniae ISU-178 ribE 17675267 1693258 1692275 984 sp: RIBD_ECOLI Escherichia coli K12 ribD 37.362.7 365 riboflavin-specific deaminase 1768 5268 1693918 1693262 657 sp:RPE_YEAST Saccharomyces cerevisiae 43.6 73.1 234 ribulose-phosphate3-epimerase S288C YJL121C rpe1 1769 5269 1695298 1693967 1332 sp:SUN_ECOLI Escherichia coli K12 sun 30.8 60.7 448 nucleolar proteinNOL1/NOP2 (eukaryotes) family 1770 5270 1696443 1695499 945 sp:FMT_PSEAE Pseudomonas aeruginosa fmt 41.6 67.9 308 methionyl-tRNAformyltransferase 1771 5271 1696972 1696466 507 sp: DEF_BACSU Bacillussubtilis 168 def 44.7 72.7 150 polypeptide deformylase 1772 5272 16991471697084 2064 sp: PRIA_ECOLI Escherichia coli priA 22.9 46.3 725primosomal protein n 1773 5273 1700397 1699177 1221 gsp: R80060Brevibacterium flavum MJ-233 99.3 99.5 407 S-adenosylmethioninesynthetase 1774 5274 1701767 1700508 1260 sp: DFP_MYCTU Mycobacteriumtuberculosis 58.0 80.9 409 DNA/pantothenate metabolism H37Rv RV1391 dfpflavoprotein 1775 5275 1702322 1702032 291 sp: YD90_MYCTU Mycobacteriumtuberculosis 70.4 87.7 81 hypothetical protein H37Rv Rv1390 1776 52761703037 1702411 627 pir: KIBYGU Saccharomyces cerevisiae guk1 39.8 74.7186 guanylate kinase 1777 5277 1703308 1702991 318 pir: B70899Mycobacterium tuberculosis 80.6 90.3 103 integration host factor H37RvRv1388 mIHF 1778 5278 1704350 1703517 834 sp: DCOP_MYCTU Mycobacteriumtuberculosis 51.8 73.6 276 orotidine-5′-phosphate H37Rv uraAdecarboxylase 1779 5279 1707697 1704359 3339 pir: SYECCP Escherichiacoli carB 53.1 77.5 1122 carbamoyl-phosphate synthase large chain 17805280 1708884 1707706 1179 sp: CARA_PSEAE Pseudomonas aeruginosa 45.470.1 381 carbamoyl-phosphate synthase ATCC 15692 carA small chain 17815281 1710357 1709017 1341 sp: PYRC_BACCL Bacillus caldolyticus DSM 40542.8 67.7 402 dihydroorotase pyrC 1782 5282 1711348 1710413 936 sp:PYRB_PSEAE Pseudomonas aeruginosa 48.6 79.7 311 aspartatecarbamoyltransferase ATCC 15692 1783 5283 1711927 1711352 576 sp:PYRR_BACCL Bacillus caldolyticus DSM 405 54.0 80.1 176 phosphoribosyltransferase or pyrR pyrimidine operon regulatory protein 1784 52841712596 1713759 1164 sp: Y00R_MYCTU Mycobacterium tuberculosis 39.7 73.4297 cell division inhibitor H37Rv Rv2216 1785 5285 1713830 1714306 4771786 5286 1714299 1714760 462 1787 5287 1714741 1714950 210 1788 52881716062 1715382 681 sp: NUSB_BACSU Bacillus subtilis nusB 33.6 69.3 137N utilization substance protein B (regulation of rRNA biosynthesis bytranscriptional antitermination) 1789 5289 1716692 1716132 561 sp:EFP_BRELA Brevibacterium lactofermentum 97.9 98.4 187 elongation factorP ATCC 13869 efp 1790 5290 1717868 1716780 1089 gp: AF124600_4Corynebacterium glutamicum 99.5 100.0 217 cytoplasmic peptidase AS019pepQ 1791 5291 1719032 1717938 1095 gp: AF124600_3 Corynebacteriumglutamicum 98.6 99.7 361 3-dehydroquinate synthase AS019 aroB 1792 52921719598 1719107 492 gp: AF124600_2 Corynebacterium glutamicum 100.0100.0 166 shikimate kinase AS019 aroK 1793 5293 1721381 1720971 411 sp:LEP3_AERHY Aeromonas hydrophila tapD 35.2 54.9 142 type IV prepilin-likeprotein specific leader peptidase 1794 5294 1721725 1721423 303 gp:SC1A2_22 Streptomyces coelicolor A3(2) 45.8 68.7 83 bacterial regulatoryprotein, arsR SC1A2.22 family 1795 5295 1721780 1722853 1074 gp:AF109162_2 Corynebacterium diphtheriae 35.9 73.2 340 ABC transporterhmuU 1796 5296 1722807 1722202 606 1797 5297 1722870 1723826 957 pir:A75169 Pyrococcus abyssi Orsay 23.6 50.7 373 iron(III) ABC transporter,PAB0349 periplasmic-binding protein 1798 5298 1723826 1724578 753 sp:FHUC_BACSU Bacillus subtilis 168 fhuC 38.3 71.7 230 ferrichrometransport ATP-binding protein 1799 5299 1725439 1724612 828 pir: D70660Mycobacterium tuberculosis 50.0 60.0 259 shikimate 5-dehydrogenase H37RvaroE 1800 5300 1726625 1725459 1167 pir: E70660 Mycobacteriumtuberculosis 41.8 70.1 395 hypothetical protein H37Rv Rv2553c 1801 53011727170 1726625 546 pir: F70660 Mycobacterium tuberculosis 52.8 69.6 161hypothetical protein H37Rv Rv2554c 1802 5302 1730048 1727385 2664 sp:SYA_THIFE Thiobacillus ferrooxidans ATCC 43.3 71.8 894 alanyl-tRNAsynthetase 33020 alaS 1803 5303 1731542 1730166 1377 sp: Y0A9_MYCTUMycobacterium tuberculosis 65.4 84.8 454 hypothetical protein H37RvRv2559c 1804 5304 1732822 1731599 1224 1805 5305 1734811 1732988 1824sp: SYD_MYCLE Mycobacterium leprae aspS 71.1 89.2 591 aspartyl-tRNAsynthetase 1806 5306 1735056 1735946 891 sp: Y0BQ_MYCTU Mycobacteriumtuberculosis 46.1 74.1 297 hypothetical protein H37Rv Rv2575 1807 53071738679 1736004 2676 sp: AMYH_YEAST Saccharomyces cerevisiae 26.1 53.6839 glucan 1,4-alpha-glucosidase S288C YIR019C sta1 1808 5308 17405691738713 1857 sp: YHGE_BACSU Bacillus subtilis yhgE 23.1 54.0 742 phageinfection protein 1809 5309 1741219 1740572 648 1810 5310 17413131741906 594 gp: SCE68_13 Streptomyces coelicolor A3(2) 29.2 62.0 192transcriptional regulator SCE68.13 1811 5311 1741893 1742606 714 18125312 1742701 1743813 1113 gp: SCE15_13 Streptomyces coelicolor A3(2)72.8 88.1 371 oxidoreductase SCE15.13c 1813 5313 1743843 1743968 1261814 5314 1744025 1744519 495 sp: SLFA_PSEAE Pseudomonas aeruginosa PAO137.1 77.6 116 NADH-dependent FMN reductase slfA 1815 5315 17448841746230 1347 sp: SDHL_ECOLI Escherichia coli K12 sdaA 46.8 71.4 462L-serine dehydratase 1816 5316 1746728 1747588 861 1817 5317 17479181746233 1686 prf: 2423362A Enterococcus casseliflavus glpO 28.4 53.9 598alpha-glycerolphosphate oxidase 1818 5318 1749276 1747990 1287 sp:SYH_STAAU Staphylococcus aureus 43.2 72.2 421 histidyl-tRNA synthetaseSR17238 hisS 1819 5319 1749963 1749325 639 gp: CJ11168X3_127Campylobacter jejuni 40.3 62.1 211 hydrolase NCTC11168 Cj0809c 1820 53201750427 1750933 507 prf: 2313309A Streptomyces chrysomallus 35.4 61.1175 cyclophilin sccypB 1821 5321 1750964 1751200 237 1822 5322 17514971752051 555 gp: AF038651_4 Corynebacterium glutamicum 98.4 100.0 128hypothetical protein ATCC 13032 orf4 1823 5323 1752186 1752527 342 18245324 1754894 1752615 2280 gp: AF038651_3 Corynebacterium glutamicum 99.999.9 760 GTP pyrophosphokinase ATCC 13032 rel 1825 5325 1755479 1754925555 gp: AF038651_2 Corynebacterium glutamicum 99.5 100.0 185 adeninephosphoribosyltransferase ATCC 13032 apt 1826 5326 1755748 1755599 150gp: AF038651_1 Corynebacterium glutamicum 98.0 98.8 49 dipeptidetransport system ATCC 13032 dciAE 1827 5327 1757228 1755486 1743 sp:Y0BG_MYCTU Mycobacterium tuberculosis 30.7 60.9 558 hypothetical proteinH37Rv Rv2585c 1828 5328 1758797 1757589 1209 sp: SECF_ECOLI Escherichiacoli K12 secF 25.9 57.2 332 protein-export membrane protein 1829 53291759707 1760336 630 1830 5330 1760734 1758803 1932 prf: 2313285ARhodobacter capsulatus secD 24.4 52.0 616 protein-export membraneprotein 1831 5331 1761367 1761005 363 sp: Y0BD_MYCLE Mycobacteriumleprae 39.6 66.0 106 hypothetical protein MLCB1259.04 1832 5332 17624981761419 1080 sp: RUVB_ECOLI Escherichia coli K12 ruvB 55.3 81.9 331holliday junction DNA helicase 1833 5333 1763134 1762517 618 sp:RUVA_MYCLE Mycobacterium leprae ruvA 45.2 74.3 210 holliday junction DNAhelicase 1834 5334 1763839 1763177 663 sp: RUVC_ECOLI Escherichia coliK12 ruvC 35.6 63.3 180 crossover junction endodeoxyribonuclease 18355335 1764742 1763990 753 sp: YEBC_ECOLI Escherichia coli K12 ORF246 49.278.4 250 hypothetical protein yebC 1836 5336 1765860 1765015 846 sp:TESB_ECOLI Escherichia coli K12 tesB 38.5 68.6 283 acyl-CoAthiolesterase 1837 5337 1765969 1766442 474 gp: SC10A5_9 Streptomycescoelicolor A3(2) 31.5 61.3 111 hypothetical protein SC10A5.09c 1838 53381766948 1766487 462 pir: H70570 Mycobacterium tuberculosis 38.2 61.2 170hypothetical protein H37Rv Rv2609c 1839 5339 1768030 1766948 1083 sp:GPI3_YEAST Saccharomyces cerevisiae 21.7 49.3 414 hexosyltransferase orN- S288C spt14 acetylglucosaminyl- phosphatidylinositol biosyntheticprotein 1840 5340 1768996 1768034 963 gp: SCL2_16 Streptomycescoelicolor A3(2) 46.4 67.8 295 acyltransferase SCL2.16c 1841 53411769678 1769022 657 pir: C70571 Mycobacterium tuberculosis 48.2 78.0 78CDP-dlacylglycerol—glycerol-3- H37Rv Rv2612c pgsA phosphatephosphatidyltransferase 1842 5342 1770340 1769681 660 pir: D70571Mycobacterium tuberculosis 54.6 78.4 194 histidine triad (HIT) familyprotein H37Rv Rv2613c 1843 5343 1772384 1770327 2058 sp: SYT2_BACSUBacillus subtilis thrZ 42.0 68.9 647 threonyl-tRNA synthetase 1844 53441773863 1772658 1206 sp: YWBN_BACSU Bacillus subtilis ywbN 34.3 61.8 400hypothetical protein 1845 5345 1773881 1774444 564 1846 5346 17744381773893 546 1847 5347 1775191 1774457 735 1848 5348 1777269 1777646 3781849 5349 1777444 1778037 594 1850 5350 1779508 1778102 1407 1851 53511780168 1779554 615 1852 5352 1780905 1780507 399 1853 5353 17815851781019 567 sp: PUAC_STRLP Streptomyces anulatus pac 36.3 64.2 190puromycin N-acetyltransferase 1854 5354 1781705 1782790 1086 1855 53551783281 1784381 1101 1856 5356 1784080 1783382 699 1857 5357 17854731782894 2580 1858 5358 1786844 1785732 1113 1859 5359 1788829 17869071923 1860 5360 1789080 1789562 483 1861 5361 1789580 1789768 189 18625362 1789746 1790057 312 1863 5363 1790889 1790461 429 1864 5364 17918421792438 597 sp: AFUC_ACTPL Actinobacillus 28.7 28.7 202 ferric transportATP-binding protein pleuropneumoniae afuC 1865 5365 1792428 1793426 9991866 5366 1793654 1793496 159 1867 5367 1793714 1794820 1107 1868 53681795202 1795621 420 1869 5369 1795591 1796181 591 gp: AF088896_20Zymomonas mobilis dfp 27.1 66.7 129 pantothenate metabolism flavoprotein1870 5370 1796186 1797049 864 1871 5371 1797350 1797769 420 1872 53721797969 1797850 120 1873 5373 1798757 1798023 735 1874 5374 17991821799406 225 1875 5375 1799473 1800366 894 1876 5376 1800604 1800449 1561877 5377 1800834 1801307 474 1878 5378 1801344 1802096 753 1879 53791802577 1802155 423 1880 5380 1802733 1803419 687 1881 5381 18034651803893 429 1882 5382 1804134 1804598 465 1883 5383 1804629 1804865 2371884 5384 1804919 1805599 681 1885 5385 1805727 1806686 960 1886 53861806917 1807396 480 1887 5387 1807433 1808113 681 1888 5388 18081371808421 285 1889 5389 1808458 1808832 375 1890 5390 1809761 1810372 612sp: TNP2_ECOLI Escherichia coli tnpR 51.1 78.0 186 transposon TN21resolvase 1891 5391 1810541 1811545 1005 1892 5392 1811564 1811938 3751893 5393 1812215 1812691 477 sp: PVH1_YEAST Saccharomyces cerevisiae29.3 51.8 164 protein-tyrosine phosphatase S288C YIR026C yvh1 1894 53941812881 1813606 726 1895 5395 1812882 1812460 423 1896 5396 18137801814517 738 gp: SCA32WHIH_6 Streptomyces coelicolor A3(2) 34.3 65.7 216sporulation transcription factor whiH 1897 5397 1814863 1815651 789 18985398 1815673 1816128 456 1899 5399 1816451 1816636 186 1900 5400 18171321817803 672 1901 5401 1817803 1818219 417 1902 5402 1818460 1818774 3151903 5403 1818798 1819166 369 1904 5404 1819954 1819748 207 1905 54051822382 1820181 2202 pir: C72285 Thermotoga maritima MSB8 22.6 55.2 545hypothetical protein TM1189 1906 5406 1822577 1824322 1746 1907 54071824371 1824589 219 1908 5408 1824784 1824927 144 1909 5409 18256061825178 429 1910 5410 1826024 1826557 534 PIR: S60891 Corynebacteriumglutamicum 63.0 75.0 166 hypothetical protein 1911 5411 1826644 1825751894 pir: S60890 Corynebacterium glutamicum 87.9 95.6 298 insertionelement (IS3 related) orf2 1912 5412 1826937 1826644 294 pir: S60889Corynebacterium glutamicum 72.3 84.2 101 insertion element (IS3 related)orf1 1913 5413 1829900 1829688 213 1914 5414 1830765 1832063 1299 19155415 1832167 1834044 1878 sp: RECJ_ERWCH Erwinia chrysanthemi recJ 24.050.6 622 single-stranded-DNA-specific exonuclease 1916 5416 18349281834149 780 1917 5417 1836675 1838324 1650 pir: T13302 Streptococcusphage phi-O1205 31.8 64.3 381 primase ORF13 1918 5418 1838349 18421373789 1919 5419 1842235 1842681 447 1920 5420 1842804 1843337 534 19215421 1843518 1845356 1839 sp: Y018_MYCPN Mycoplasma pneumoniae ATCC 22.144.7 620 helicase 29342 yb95 1922 5422 1845483 1845857 375 1923 54231845872 1846207 336 pir: T13144 Bacteriophage N15 gene57 36.7 64.2 109phage N15 protein gp57 1924 5424 1846698 1846333 366 1925 5425 18473151847932 618 1926 5426 1847938 1848474 537 1927 5427 1848509 1849036 5281928 5428 1848988 1849785 798 1929 5429 1849781 1849966 186 1930 54301850035 1850406 372 1931 5431 1850415 1849978 438 1932 5432 18510491850474 576 1933 5433 1851220 1852440 1221 gp: SPAPJ760_2Schizosaccharomyces pombe 28.7 49.8 422 actin binding protein with SH3SPAPJ760.02c domains 1934 5434 1851473 1852324 852 1935 5435 18524791853873 1395 1936 5436 1854261 1854854 594 1937 5437 1855058 1855237 1801938 5438 1855532 1856788 1257 gp: SC5C7_14 Streptomyces coelicolor 23.652.5 347 ATP/GTP binding protein SC5C7.14 1939 5439 1856885 1858738 18541940 5440 1858763 1860727 1965 sp: CLPA_ECOLI Escherichia coli K12 clpA30.2 61.0 630 ATP-dependent Clp proteinase ATP- binding subunit 19415441 1860752 1861225 474 1942 5442 1861320 1861475 156 1943 5443 18618421861519 324 1944 5444 1862088 1862399 312 1945 5445 1862945 1865299 2355sp: PCRA_STAAU Staphylococcus aureus SA20 21.4 45.9 693 ATP-dependenthelicase pcrA 1946 5446 1865265 1865822 558 1947 5447 1865842 1866219378 1948 5448 1866328 1866792 465 1949 5449 1866832 1867095 264 19505450 1867098 1867874 777 gp: SCH17_7 Streptomyces coelicolor A3(2) 25.947.8 224 hypothetical protein SCH17.07c 1951 5451 1867886 1868587 702prf: 2514444Y Bacteriophage phi-C31 gp52 31.7 61.5 208 deoxynucleotidemonophosphate kinase 1952 5452 1868895 1868671 225 1953 5453 18710921868927 2166 1954 5454 1871373 1871101 273 1955 5455 1877886 18713806507 1956 5456 1878312 1879400 1089 prf: 2403350A Corynebacteriumglutamicum 99.2 99.7 363 type II 5-cytosoine ATCC 13032 cglIMmethyltransferase 1957 5457 1879412 1880485 1074 pir: A55225Corynebacterium glutamicum 99.7 99.7 358 type II restrictionendonuclease ATCC 13032 cglIR 1958 5458 1883990 1882470 1521 1959 54591884936 1884220 717 1960 5460 1885230 1887047 1818 gp: SC1A2_16Streptomyces coelicolor A3(2) 24.6 45.8 504 hypothetical proteinSC1A2.16c 1961 5461 1887405 1887590 186 1962 5462 1888038 1887688 351gp: AE001973_4 Deinococcus radiodurans 46.7 70.0 90 SNF2/Rad54helicase-related DR1258 protein 1963 5463 1889094 1888231 864 pir:T13226 Lactobacillus phage phi-gle 33.1 56.4 163 hypothetical proteinRorf232 1964 5464 1889530 1889859 330 1965 5465 1891707 1890028 1680 gp:AF188935_16 Bacillus anthracis pXO2-16 20.7 47.9 537 hypotheticalprotein 1966 5466 1893037 1891832 1206 1967 5467 1894680 1893388 12931968 5468 1897231 1894739 2493 1969 5469 1899158 1897374 1785 sp:CLPB_ECOLI Escherichia coli clpB 25.3 52.5 724 endopeptidase ClpATP-binding chain B 1970 5470 1899853 1899233 621 1971 5471 19009161899804 1113 1972 5472 1901911 1901066 846 1973 5473 1901975 1902955 9811974 5474 1902883 1902005 879 1975 5475 1903028 1903225 198 1976 54761905878 1903113 2766 pir: S23647 Homo sapiens numA 20.1 49.1 1004nuclear mitotic apparatus protein 1977 5477 1906572 1905973 600 19785478 1907914 1906664 1251 1979 5479 1908660 1907965 696 1980 54801909498 1908785 714 1981 5481 1910508 1909501 1008 1982 5482 19123001910642 1659 1983 5483 1913820 1912333 1488 1984 5484 1914371 1913973399 1985 5485 1916233 1914725 1509 1986 5486 1916374 1916733 360 19875487 1916944 1917165 222 1988 5488 1917640 1917329 312 1989 5489 19182081917564 645 1990 5490 1919461 1918703 759 1991 5491 1920194 1919646 5491992 5492 1921276 1920347 930 1993 5493 1925390 1925695 306 1994 54941925682 1926038 357 1995 5495 1926010 1921547 4464 pir: T03099 Susscrofa domestica 23.2 49.2 1408 submaxillary apomucin 1996 5496 19268371926259 579 1997 5497 1928189 1927245 945 1998 5498 1928211 1928381 171sp: MTE1_ECOLI Escherichia coli ecoR1 42.6 65.6 61 modificationmethylase 1999 5499 1928534 1928908 375 2000 5500 1930879 1929059 18212001 5501 1931190 1930990 201 2002 5502 1931888 1931421 468 2003 55031932315 1931935 381 pir: H70638 Mycobacterium tuberculosis 38.6 58.8 114hypothetical protein H37Rv Rv1956 2004 5504 1932879 1932373 507 20055505 1934358 1933522 837 2006 5506 1935912 1934971 942 sp: Y137_METJAMethanococcus jannaschii 27.1 54.6 328 hypothetical protein MJ0137 20075507 1936226 1936849 624 2008 5508 1937202 1937411 210 2009 5509 19380191937486 534 2010 5510 1938945 1940135 1191 2011 5511 1939064 1938531 5342012 5512 1940257 1940844 588 2013 5513 1941107 1941550 444 2014 55141942484 1941732 753 2015 5515 1942510 1942812 303 2016 5516 19430951943310 216 2017 5517 1943345 1943653 309 2018 5518 1943680 1944564 8852019 5519 1945435 1944608 828 prf: 2509434A Enterococcus faecalis esp23.0 44.1 304 surface protein 2020 5520 1945891 1945595 297 2021 55211946332 1945952 381 2022 5522 1947037 1946609 429 2023 5523 19486501947070 1581 sp: CSP1_CORGL Corynebacterium glutamicum 30.7 54.4 270major secreted protein PS1 protein (Brevibacterium flavum) ATCCprecursor 17965 csp1 2024 5524 1951450 1949021 2430 2025 5525 19524851951619 867 2026 5526 1954822 1952546 2277 sp: TOP3_ECOLI Escherichiacoli topB 23.8 50.9 597 DNA topoisomerase III 2027 5527 1958287 19562032085 2028 5528 1959340 1958450 891 2029 5529 1960196 1959765 432 20305530 1961114 1960371 744 2031 5531 1963000 1961114 1887 sp: CSP1_CORGLCorynebacterium glutamicum 29.7 54.7 344 major secreted protein PS1protein (Brevibacterium flavum) ATCC precursor 17965 csp1 2032 55321963429 1963139 291 2033 5533 1964743 1963514 1230 2034 5534 19659021964727 1176 2035 5535 1966267 1965911 357 2036 5536 1966301 1966984 684sp: NUC_STAAU Staphylococcus aureus nuc 30.4 57.7 227 thermonuclease2037 5537 1967435 1967289 147 2038 5538 1967604 1968167 564 2039 55391968264 1969715 1452 2040 5540 1969745 1970203 459 2041 5541 19702541971474 1221 2042 5542 1971672 1973090 1419 2043 5543 1973147 1973737591 2044 5544 1973809 1974204 396 2045 5545 1974267 1974503 237 20465546 1975171 1975794 624 prf: 2313347B Shewanella sp. ssb 24.9 59.1 225single stranded DNA-binding protein 2047 5547 1975916 1976494 579 20485548 1976522 1976983 462 2049 5549 1977043 1977549 507 2050 5550 19777421978329 588 2051 5551 1978389 1978721 333 2052 5552 1978660 1979217 5582053 5553 1979239 1979808 570 2054 5554 1979974 1980885 912 sp:S24D_ANOGA Anopheles gambiae AgSP24D 25.7 52.6 249 serine protease 20555555 1980965 1981657 693 2056 5556 1981663 1982028 366 2057 5557 19820711982817 747 2058 5558 1982091 1981912 180 2059 5559 1983186 1983548 3632060 5560 1983611 1983883 273 2061 5561 1983918 1984181 264 2062 55621984217 1984450 234 2063 5563 1984387 1984728 342 2064 5564 19850921985364 273 2065 5565 1985373 1985071 303 2066 5566 1986590 1985442 1149sp: VINT_BPML5 Mycobacterium phage L5 int 29.6 55.9 406 integrase 20675567 1987896 1987507 390 gsp: R23011 Brevibacterium lactofermentum 83.994.4 124 transposase (divided) CGL2005 ISaB1 2068 5568 1988303 1987887417 gsp: R23011 Brevibacterium lactofermentum 70.9 84.6 117 transposase(divided) CGL2005 ISaB1 2069 5569 1988383 1988589 207 2070 5570 19884831988370 114 gsp: R21601 Brevibacterium lactofermentum 80.7 96.8 31transposition repressor CGL2005 ISaB1 2071 5571 1988664 1988530 135 pir:S60889 Corynebacterium glutamicum 74.4 88.4 43 insertion element (IS3related) orf1 2072 5572 1989605 1988778 828 gp: SCJ11_12 Streptomycescoelicolor A3(2) 31.1 53.7 270 transposase SCJ11.12 2073 5573 19906671991020 354 2074 5574 1990764 1989874 891 2075 5575 1991620 1991189 4322076 5576 1992538 1991795 744 2077 5577 1994121 1992538 1584 sp:CSP1_CORGL Corynebacterium glutamicum 25.0 37.0 153 major secretedprotein PS1 protein (Brevibacterium flavum) ATCC precursor 17965 csp12078 5578 1995294 1994608 687 sp: VINT_BPML5 Mycobacterium phage L5 int28.7 56.1 223 integrase 2079 5579 1996088 1995783 306 pir: F64546Helicobacter pylori 26695 39.8 76.1 88 sodium-dependent transporterHP0214 2080 5580 1996106 1996537 432 sp: YXAA_BACSU Bacillus subtilisyxaA 48.9 81.5 92 hypothetical protein 2081 5581 1996768 1997112 3452082 5582 1997168 1997503 336 2083 5583 1997545 1998240 696 pir: C70968Mycobacterium tuberculosis 33.5 64.4 233 riboflavin biosynthesis proteinH37Rv Rv2671 ribD 2084 5584 1998289 1999542 1254 pir: E70968Mycobacterium tuberculosis 42.5 71.9 384 potential membrane proteinH37Rv Rv2673 2085 5585 1999542 1999949 408 gp: AF128264_2 Streptococcusgordonii msrA 41.3 67.5 126 methionine sulfoxide reductase 2086 55862000132 1999707 426 2087 5587 2001216 2000521 696 pir: H70968Mycobacterium tuberculosis 55.2 77.2 232 hypothetical protein H37RvRv2676c 2088 5588 2001489 2002112 624 pir: C70528 Mycobacteriumtuberculosis 55.7 78.6 201 hypothetical protein H37Rv Rv2680 2089 55892002072 2003334 1263 sp: RND_HAEIN Haemophilus influenzae Rd 25.9 52.8371 ribonuclease D KW20 HI0390 rnd 2090 5590 2005309 2003402 1908 gp:AB026631_1 Streptomyces sp. CL190 dxs 55.3 78.5 6181-deoxy-D-xylulose-5-phosphate synthase 2091 5591 2006697 2005462 1236pir: E72298 Thermotoga maritima MSB8 25.4 52.3 472 RNA methyltransferaseTM1094 2092 5592 2006698 2006979 282 2093 5593 2007637 2006777 861 pir:C70530 Mycobacterium tuberculosis 38.1 62.7 268 hypothetical proteinH37Rv Rv2696c 2094 5594 2008184 2007738 447 sp: DUT_STRCO Streptomycescoelicolor A3(2) 55.0 82.1 140 deoxyuridine 5′-triphosphate SC2E9.09 dutnucleotidohydrolase 2095 5595 2008250 2008798 549 pir: E70530Mycobacterium tuberculosis 46.0 70.7 150 hypothetical protein H37RvRv2698 2096 5596 2009082 2008876 207 2097 5597 2009570 2009280 291 pir:F70530 Mycobacterium tuberculosis 58.0 81.0 100 hypothetical proteinH37Rv Rv2699c 2098 5598 2010539 2009724 816 sp: SUHB_ECOLI Escherichiacoli K12 suhB 38.4 68.2 198 extragenic suppressor protein 2099 55992010555 2011382 828 sp: PPGK_MYCTU Mycobacterium tuberculosis 54.4 80.2248 polyphosphate glucokinase H37Rv RV2702 ppgK 2100 5600 20118632013356 1494 prf: 2204286A Corynebacterium glutamicum 98.0 98.6 500sigma factor or RNA polymerase sigA transcription factor 2101 56012015496 2014162 1335 sp: YRKO_BACSU Bacillus subtilis yrkO 23.9 51.4 422hypothetical membrane protein 2102 5602 2016121 2015585 537 2103 56032017966 2016257 1710 sp: Y065_MYCTU Mycobacterium tuberculosis 61.3 80.8578 hypothetical protein H37Rv Rv2917 2104 5604 2018119 2018754 636 pir:H70531 Mycobacterium tuberculosis 32.3 59.1 127 hypothetical membraneprotein H37Rv Rv2709 2105 5605 2018202 2017966 237 pir: G70531Mycobacterium tuberculosis 65.8 85.5 76 hypothetical protein H37RvRv2708c 2106 5606 2018744 2020276 1533 gp: SCH5_8 Streptomycescoelicolor A3(2) 33.5 61.2 523 transferase SCH5.08c 2107 5607 20202932020724 432 prf: 2204286C Corynebacterium glutamicum 97.2 100.0 144hypothetical protein ATCC 13869 ORF1 2108 5608 2022266 2022949 684 pir:I40339 Corynebacterium glutamicum 98.7 99.6 228 iron dependent repressoror ATCC 13869 dtxR diphtheria toxin repressor 2109 5609 2022546 2022313234 GP: AF010134_1 Streptomyces aureofaciens 62.0 64.0 77 putativesporulation protein 2110 5610 2022959 2023945 987 sp: GALE_BRELACorynebacterium glutamicum 99.1 99.1 329 UDP-glucose 4-epimerase ATCC13869 (Brevibacterium lactofermentum) galE 2111 5611 2025270 20239481323 2112 5612 2025423 2026379 957 pir: E70532 Mycobacteriumtuberculosis 45.3 79.0 305 hypothetical protein H37Rv Rv2714 2113 56132026494 2029043 2550 sp: MTR4_YEAST Saccharomyces cerevisiae 24.4 50.7661 ATP-dependent RNA helicase YJL050W dob1 2114 5614 2029177 2030157981 sp: OXYR_ECOLI Escherichia coli oxyR 35.8 65.6 299 hydrogenperoxide-inducible genes activator 2115 5615 2031365 2030277 1089 21165616 2031478 2035383 3906 sp: HRPA_ECOLI Escherichia coli hrpA 49.2 76.21298 ATP-dependent helicase 2117 5617 2035880 2035431 450 gp: SCAJ4870_3Streptomyces clavuligerus nrdR 61.4 86.2 145 regulatory protein 21185618 2036409 2035990 420 2119 5619 2036812 2037507 696 sp: LEXA_BACSUBacillus subtilis dinR 46.9 71.6 222 SOS regulatory protein 2120 56202037815 2038591 777 sp: GATR_ECOLI Escherichia coli K12 gatR 33.9 67.8245 galactitol utilization operon repressor 2121 5621 2038591 2039550960 gp: SCE22_14 Streptomyces coelicolor A3(2) 27.2 55.6 320phosphofructokinase (fructose 1- SCE22.14c phosphate kinase) 2122 56222041321 2039618 1704 sp: PT1_BACST Bacillus stearothermophilus ptsI 34.364.0 592 phosphoenolpyruvate-protein phosphotransferase 2123 56232041728 2042519 792 sp: GLPR_ECOLI Escherichia coli K12 glpR 26.7 62.6262 glycerol-3-phosphate regulon repressor 2124 5624 2042519 2043508 990sp: K1PF_RHOCA Rhodobacter capsulatus fruK 33.0 55.7 3451-phosphofructokinase or 6- phosphofructokinase 2125 5625 20437362045571 1836 sp: PTFB_ECOLI Escherichia coli K12 fruA 43.0 69.6 549 PTSsystem, fructose-specific IIBC component 2126 5626 2045762 2046028 267sp: PTHP_BACST Bacillus stearothermophilus XL- 37.0 71.6 81phosphocarrier protein 65-6 ptsH 2127 5627 2047295 2046714 582 2128 56282048606 2047320 1287 sp: PYRP_BACCL Bacillus caldolyticus pyrP 39.1 70.5407 uracil permease 2129 5629 2050107 2048650 1458 gp: AF145049_8Streptomyces fradiae orf11* 54.4 80.0 419 ATP/GTP-binding protein 21305630 2050321 2051106 786 2131 5631 2051306 2051842 537 2132 5632 20526752051845 831 sp: DAPF_HAEIN Haemophilus influenzae Rd 33.5 64.7 269diaminopimelate epimerase KW20 HI0750 dapF 2133 5633 2053586 2052684 903sp: MIAA_ECOLI Escherichia coli K12 miaA 40.0 68.7 300 tRNA delta-2-isopentenylpyrophosphate transferase 2134 5634 2054283 2053609 675 21355635 2054403 2055761 1359 pir: B70506 Mycobacterium tuberculosis 48.575.7 445 hypothetical protein H37Rv Rv2731 2136 5636 2055743 20547241020 2137 5637 2055765 2056787 1023 2138 5638 2057788 2057120 669 pir:C70506 Mycobacterium tuberculosis 29.0 63.7 190 hypothetical membraneprotein H37Rv Rv2732c 2139 5639 2059420 2057855 1566 sp: Y195_MYCLEMycobacterium leprae 68.4 86.4 494 hypothetical protein B2235_C2_1952140 5640 2059774 2060499 726 sp: GLUA_CORGL Corynebacterium glutamicum99.6 99.6 242 glutamate transport ATP-binding ATCC 13032 gluA protein2141 5641 2060414 2060196 219 GSP: Y75358 Neisseria gonorrhoeae 66.073.0 71 Neisserial polypeptides predicted to be useful antigens forvaccines and diagnostics 2142 5642 2061629 2062312 684 sp: GLUC_CORGLCorynebacterium glutamicum 100.0 100.0 225 glutamate transport systemATCC 13032 gluC permease protein 2143 5643 2062441 2063259 819 sp:GLUD_CORGL Corynebacterium glutamicum 99.3 99.6 273 glutamate transportsystem (Brevibacterium flavum) ATCC permease protein 13032 gluD 21445644 2063894 2063298 597 sp: RECX_MYCLE Mycobacterium leprae recX 34.566.9 142 regulatory protein 2145 5645 2065627 2065394 234 pir: A70878Mycobacterium tuberculosis 40.3 71.6 67 hypothetical protein H37RvRv2738c 2146 5646 2066404 2065667 738 2147 5647 2066566 2067141 576 sp:BIOY_BACSH Bacillus sphaericus bioY 33.0 61.4 197 biotin synthase 21485648 2067168 2067866 699 sp: POTG_ECOLI Escherichia coli K12 potG 33.269.5 223 putrescine transport ATP-binding protein 2149 5649 20678662068474 609 pir: F69742 Bacillus subtilis ybaF 24.6 58.8 228hypothetical membrane protein 2150 5650 2068703 2069392 690 pir: B60176Mycobacterium tuberculosis 41.7 78.5 228 hypothetical protein 2151 56512069383 2068556 828 sp: 35KD_MYCTU Mycobacterium tuberculosis 72.5 89.6269 hypothetical protein (35 kD protein) H37Rv RV2744C 2152 5652 20699362069616 321 pir: H70878 Mycobacterium tuberculosis 54.2 78.3 83regulator (DNA-binding protein) H37Rv Rv2745c 2153 5653 2070512 2069997516 sp: CINA_STRPN Streptococcus pneumoniae R6X 41.8 68.5 165 competencedamage induced cinA proteins 2154 5654 2071121 2070519 603 prf: 2421334DStreptococcus pyogenes pgsA 38.8 72.5 160 phosphotidylglycerophosphatesynthase 2155 5655 2071315 2071599 285 pir: T10688 Arabidopsis thaliana24.8 52.1 117 hypothetical protein ATSP: T16|18.20 2156 5656 20716242071740 117 gp: AF071810_1 Streptococcus pneumoniae 60.0 70.0 30 surfaceprotein (Peumococcal DBL5 pspA surface protein A) 2157 5657 20720662072878 813 2158 5658 2072905 2071799 1107 prf: 2119295D Escherichiacoli terC 31.0 59.8 358 tellurite resistance protein 2159 5659 20760562073294 2763 sp: SP3E_BACSU Bacillus subtilis 168 spoIIIE 38.0 64.6 845stage III sporulation protein E 2160 5660 2077024 2076392 633 gp:SC4G6_14 Streptomyces coelicolor A3(2) 33.3 61.0 216 hypotheticalprotein SC4G6.14 2161 5661 2079275 2077122 2154 sp: YOR4_CORGLCorynebacterium glutamicum 99.1 99.4 645 hypothetical protein ATCC 13032orf4 2162 5662 2081136 2080387 750 sp: YDAP_BRELA Corynebacteriumglutamicum 99.2 99.6 250 hypothetical protein (Brevibacteriumlactofermentum) ATCC 13869 orf2 2163 5663 2082115 2082813 699 2164 56642082368 2082105 264 2165 5665 2085190 2082932 2259 prf: 2217311AStreptomyces antibioticus gpsI 65.4 85.3 742 guanosine pentaphosphatesynthetase 2166 5666 2085702 2085436 267 pir: F69700 Bacillus subtilisrpsO 64.0 88.8 89 30S ribosomal protein S15 2167 5667 2086826 2085879948 prf: 2518365A Leishmania major 35.1 63.3 319 nucleoside hydrolase2168 5668 2087941 2086919 1023 sp: RIBF_CORAM Corynebacterium 56.2 79.0329 bifunctional protein (riboflavin kinase ammoniagenes ATCC 6872 ribFand FAD synthetase) 2169 5669 2087973 2088863 891 sp: TRUB_BACSUBacillus subtilis 168 truB 32.7 61.7 303 tRNA pseudouridine synthase B2170 5670 2088181 2087954 228 PIR: PC4007 Corynebacterium 65.0 73.0 47hypothetical protein ammoniagenes 2171 5671 2089868 2089218 651 gp:SC5A7_23 Streptomyces coelicolor A3(2) 42.2 62.5 237 hypotheticalprotein SC5A7.23 2172 5672 2090664 2089861 804 pir: B70885 Mycobacteriumtuberculosis 46.9 68.9 273 phosphoesterase H37Rv Rv2795c 2173 56732092055 2090751 1305 pir: G70693 Mycobacterium tuberculosis 51.0 78.8433 DNA damaged inducible protein f H37Rv Rv2836c dinF 2174 5674 20930462092051 996 pir: H70693 Mycobacterium tuberculosis 36.7 70.8 308hypothetical protein H37Rv Rv2837c 2175 5675 2093501 2093055 447 sp:RBFA_BACSU Bacillus subtilis 168 rbfA 32.4 70.4 108 ribosome-bindingfactor A 2176 5676 2096723 2093712 3012 sp: IF2_STIAU Stigmatellaaurantiaca DW4 infB 37.7 62.9 1103 translation initiation factor IF-22177 5677 2097179 2096844 336 gp: SC5H4_29 Streptomyces coelicolor A3(2)44.6 66.3 83 hypothetical protein SC5H4.29 2178 5678 2098375 2097380 996sp: NUSA_BACSU Bacillus subtilis 168 nusA 42.3 71.0 352 n-utilizationsubstance protein (transcriptional termination/antitermination factor)2179 5679 2098562 2099815 1254 2180 5680 2098945 2098412 534 pir: E70588Mycobacterium tuberculosis 34.6 65.5 165 hypothetical protein H37RvRv2842c 2181 5681 2100240 2101841 1602 sp: DPPE_BACSU Bacillus subtilis168 dppE 25.3 60.9 534 peptide-binding protein 2182 5682 2102023 2102946924 sp: DPPB_ECOLI Escherichia coli K12 dppB 37.7 69.4 337peptidetransport system permease 2183 5683 2102975 2103973 999 prf:1709239C Bacillus subtilis spo0KC 38.4 69.2 292 oligopeptide permease2184 5684 2103973 2105703 1731 pir: H70788 Mycobacterium tuberculosis57.6 81.3 552 peptidetransport system ABC- H37Rv Rv3663c dppDtransporter ATP-binding protein 2185 5685 2107564 2105801 1764 sp:SYP_MYCTU Mycobacterium tuberculosis 67.0 84.6 578 prolyl-tRNAsynthetase H37Rv Rv2845c proS 2186 5686 2107652 2108386 735 gp: SCC30_5Streptomyces coelicolor A3(2) 39.5 65.0 243 hypothetical proteinSCC30.05 2187 5687 2109147 2108389 759 sp: BCHD_RHOSH Rhodobactersphaeroides ATCC 32.4 60.7 37 magnesium-chelatase subunit 17023 bchD2188 5688 2110255 2109155 1101 prf: 2503462AA Heliobacillus mobilis bchI46.5 69.6 342 magnesium-chelatase subunit 2189 5689 2111183 2110434 750prf: 2108318B Propionibacterium freudenreichii 49.0 73.8 237uroporphyrinogen III cobA methyltransferase 2190 5690 2111238 21126591422 sp: YPLC_CLOPE Clostridium perfringens NCIB 41.2 68.7 488hypothetical protein 10662 ORF2 2191 5691 2113616 2112717 900 gp:SC5H1_10 Streptomyces coelicolor A3(2) 35.1 62.3 151 hypotheticalprotein SC5H1.10c 2192 5692 2115761 2116774 1014 pir: A70590Mycobacterium tuberculosis 37.6 65.7 338 hypothetical protein H37RvRv2854 2193 5693 2116916 2118310 1395 sp: GSHR_BURCE Burkholderiacepacia AC1100 53.0 76.6 466 glutathione reductase gor 2194 5694 21179562117015 942 2195 5695 2118607 2119080 474 2196 5696 2119139 2119495 3572197 5697 2119628 2120356 729 2198 5698 2121147 2120359 789 sp:AMPM_ECOLI Escherichia coli K12 map 47.2 75.8 252 methionineaminopeptidase 2199 5699 2123161 2121296 1866 prf: 2224268A Streptomycesclavuligerus pcbR 27.3 56.5 630 penicillin binding protein 2200 57002123848 2123219 630 prf: 2518330B Corynebacterium diphtheriae 44.0 72.2216 response regulator (two-component chrA system response regulator)2201 5701 2124996 2123848 1149 prf: 2518330A Corynebacterium diphtheriae29.5 56.8 424 two-component system sensor chrS histidine kinase 22025702 2125089 2126045 957 gp: AE001863_70 Deinococcus radiodurans 24.458.1 360 hypothetical membrane protein DRA0279 2203 5703 2126064 2126753690 prf: 2420410P Bacillus subtilis 168 yvrO 37.3 71.1 225 ABCtransporter 2204 5704 2127087 2126926 162 2205 5705 2128483 2127350 1134sp: GCPE_ECOLI Escherichia coli K12 gcpE 44.3 73.8 359 hypotheticalprotein (gcpE protein) 2206 5706 2128850 2129461 612 2207 5707 21298802128669 1212 pir: G70886 Mycobacterium tuberculosis 43.0 73.6 405hypothetical membrane protein H37Rv Rv2869c 2208 5708 2130306 2130950645 GSP: Y37145 Chlamydia trachomatis 36.0 43.0 147 polypeptides can beused as vaccines against Chlamydia trachomatis 2209 5709 2131078 21299031176 sp: DXR_ECOLI Escherichia coli K12 dxr 22.8 42.0 3121-deoxy-D-xylulose-5-phosphate reductoisomerase 2210 5710 21313222131762 441 2211 5711 2131726 2131247 480 2212 5712 2133402 2131825 15782213 5713 2134260 2133406 855 pir: B72334 Thermotoga maritima MSB8 37.175.1 245 ABC transporter ATP-binding protein TM0793 2214 5714 21355512134454 1098 sp: YS80_MYCTU Mycobacterium tuberculosis 66.0 78.0 356pyruvate formate-lyase 1 activating H37Rv enzyme 2215 5715 21358842136141 258 pir: A70801 Mycobacterium tuberculosis 41.5 74.5 94hypothetical membrane protein H37Rv Rv3760 2216 5716 2137089 2136235 855sp: CDSA_PSEAE Pseudomonas aeruginosa 33.3 56.5 294 phosphatidatecytidylyltransferase ATCC 15692 cdsA 2217 5717 2137840 2137286 555 sp:RRF_BACSU Bacillus subtilis 168 frr 47.0 84.3 185 ribosome recyclingfactor 2218 5718 2138664 2137936 729 prf: 2510355C Pseudomonasaeruginosa pyrH 28.4 43.1 109 uridylate kinase 2219 5719 2138994 2139854861 2220 5720 2139827 2139003 825 sp: EFTS_STRCO Streptomyces coelicolorA3(2) 49.6 76.8 280 elongation factor Ts SC2E1.42 tsf 2221 5721 21408862140071 816 pir: A69699 Bacillus subtilis rpsB 54.7 83.5 254 30Sribosomal protein S2 2222 5722 2141257 2141760 504 sp: YS91_MYCTUMycobacterium tuberculosis 46.0 58.0 120 hypothetical protein H37RvRv2891 2223 5723 2142686 2141763 924 prf: 2417318A Proteus mirabilisxerD 40.1 68.7 297 site-specific recombinase 2224 5724 2144066 21428851182 sp: YX27_MYCTU Mycobacterium tuberculosis 39.8 66.8 395hypothetical protein H37Rv Rv2896c 2225 5725 2145586 2144066 1521 sp:YX28_MYCTU Mycobacterium tuberculosis 46.6 75.8 504 Mg(2+) chelatasefamily protein H37Rv Rv2897c 2226 5726 2145941 2145576 366 sp:YX29_MYCTU Mycobacterium tuberculosis 40.3 72.3 119 hypothetical proteinH37Rv Rv2898c 2227 5727 2146566 2146264 303 sp: YT01_MYCTU Mycobacteriumtuberculosis 68.3 96.0 101 hypothetical protein H37Rv Rv2901c 2228 57282147192 2146566 627 sp: RNH2_HAEIN Haemophilus influenzae Rd 42.6 69.5190 ribonuclease HII HI1059 rnhB 2229 5729 2147231 2148022 792 2230 57302148046 2147261 786 prf: 2514288H Streptomyces lividans TK21 32.3 61.1285 signal peptidase sipY 2231 5731 2148231 2149166 936 prf: 2510361AStaphylococcus aureus sirA 25.4 59.1 323 Fe-regulated protein 2232 57322149571 2149359 213 2233 5733 2149972 2149634 339 sp: RL19_BACSTBacillus stearothermophilus rplS 70.3 88.3 111 50S ribosomal protein L192234 5734 2150335 2150997 663 sp: THIE_BACSU Bacillus subtilis 168 thiE28.4 60.9 225 thiamine phosphate pyrophosphorylase 2235 5735 21510392152118 1080 gp: SC6E10_1 Streptomyces coelicolor A3(2) 34.0 64.1 376oxidoreductase SC6E10.01 2236 5736 2152135 2152329 195 sp: THIS_ECOLIEscherichia coli K12 thiS 37.1 74.2 62 thiamine biosynthetic enzyme thiS(thiG1) protein 2237 5737 2152334 2153113 780 sp: THIG_ECOLI Escherichiacoli K12 thiG 48.2 76.9 251 thiamine biosynthetic enzyme thiG protein2238 5738 2153058 2154191 1134 prf: 2417383A Emericella nidulans cnxF30.2 56.8 437 molybdopterin biosynthesis protein 2239 5739 21567332154460 2274 sp: TEX_BORPE Bordetella pertussis TOHAMA I 56.6 78.7 776transcriptional accessory protein tex 2240 5740 2157721 2156747 975 pir:A36940 Bacillus subtilis 168 degA 27.0 65.3 334 sporulation-specificdegradation regulator protein 2241 5741 2159181 2157754 1428 pir: H72105Chlamydophila pneumoniae 45.8 78.3 456 dicarboxylase translocator CWL029ybhl 2242 5742 2159237 2159019 219 prf: 2108268A Spinacia oleraceachloroplast 40.0 80.0 65 2-oxoglutarate/malate translocator 2243 57432160537 2159287 1251 sp: PCAB_PSEPU Pseudomonas putida pcaB 39.1 66.3350 3-carboxy-cis, cis-muconate cycloisomerase 2244 5744 2160670 216076899 2245 5745 2161503 2161111 393 2246 5746 2162196 2161507 690 2247 57472163014 2162196 819 sp: TRMD_ECOLI Escherichia coli K12 trmD 34.8 64.8273 tRNA (guanine-N1)- methyltransferase 2248 5748 2163098 2163745 648gp: SCF81_27 Streptomyces coelicolor A3(2) 30.5 57.6 210 hypotheticalprotein SCF81.27 2249 5749 2164260 2163748 513 sp: RIMM_MYCLEMycobacterium leprae 52.3 72.1 172 16S rRNA processing proteinMLCB250.34. rimM 2250 5750 2164390 2164737 348 pir: B71881 Helicobacterpylori J99 jhp0839 29.0 66.7 69 hypothetical protein 2251 5751 21653092164815 495 pir: C47154 Bacillus subtilis 168 rpsP 47.0 79.5 83 30Sribosomal protein S16 2252 5752 2165523 2166098 576 pir: T14151 Musmusculus inv 32.1 61.7 196 inversin 2253 5753 2166990 2166124 867 prf:2512328G Streptococcus agalactiae cylB 26.6 69.1 256 ABC transporter2254 5754 2167865 2166990 876 prf: 2220349C Pyrococcus horikoshll OT3mtrA 35.5 63.8 318 ABC transporter 2255 5755 2169584 2167944 1641 sp:SR54_BACSU Bacillus subtilis 168 ffh 58.7 78.2 559 signal recognitionparticle protein 2256 5756 2170426 2171058 633 2257 5757 2171715 2172131417 2258 5758 2172209 2172877 669 2259 5759 2175288 2173759 1530 sp:FTSY_ECOLI Escherichia coli K12 ftsY 37.0 66.1 505 cell division protein2260 5760 2176046 2175888 159 2261 5761 2176402 2177103 702 2262 57622179502 2176110 3393 sp: AMYH_YEAST Saccharomyces cerevisiae 22.4 46.21144 glucan 1,4-alpha-glucosidase or S288C YIR019C sta1 glucoamylaseS1/S2 precursor 2263 5763 2180918 2181880 963 2264 5764 2183092 21796283465 sp: Y06B_MYCTU Mycobacterium tuberculosis 48.3 72.6 1206 chromosomesegregation protein H37Rv Rv2922c smc 2265 5765 2183391 2183110 282 sp:ACYP_MYCTU Mycobacterium tuberculosis 51.1 73.9 92 acylphosphatase H37RvRV2922.1C 2266 5766 2185258 2183405 1854 2267 5767 2186208 2185351 858sp: YFER_ECOLI Escherichia coli K12 yfeR 23.9 60.0 305 transcriptionalregulator 2268 5768 2186299 2187129 831 pir: S72748 Mycobacterium leprae39.3 73.5 257 hypothetical membrane protein MLCL581.28c 2269 57692187160 2187342 183 2270 5770 2187679 2187233 447 2271 5771 21883062187692 615 gp: DNINTREG_3 Dichelobacter nodosus gep 46.8 76.6 188cation efflux system protein 2272 5772 2189170 2188313 858 sp: FPG_ECOLIEscherichia coli K12 mutM or 36.1 66.7 285 formamidopyrimidine-DNA fpgglycosylase 2273 5773 2189906 2189166 741 pir: B69693 Bacillus subtilis168 rncS 40.3 76.5 221 ribonuclease III 2274 5774 2190439 2189906 534sp: Y06F_MYCTU Mycobacterium tuberculosis 35.8 62.5 176 hypotheticalprotein H37Rv Rv2926c 2275 5775 2191328 2190540 789 sp: Y06G_MYCTUMycobacterium tuberculosis 50.0 76.9 238 hypothetical protein H37RvRv2927c 2276 5776 2191522 2193165 1644 prf: 2104260G Streptomycesverticillus 28.3 55.6 559 transport protein 2277 5777 2193165 21946941530 sp: CYDC_ECOLI Escherichia coli K12 cydC 26.6 58.8 541 ABCtransporter 2278 5778 2196883 2198004 1122 gp: SC9C7_2 Streptomycescoelicolor A3(2) 35.3 62.6 388 hypothetical protein SC9C7.02 2279 57792198447 2198007 441 2280 5780 2198475 2199758 1284 pir: A72322Thermotoga maritima MSB8 21.0 43.7 405 hypothetical protein TM0896 22815781 2199808 2201070 1263 sp: HIPO_CAMJE Campylobacter jejuni ATCC 32.964.3 353 peptidase 43431 hipO 2282 5782 2201408 2201073 336 pir: S38197Arabidopsis thaliana SUC1 27.1 51.9 133 sucrose transport protein 22835783 2201584 2201450 135 2284 5784 2201869 2201594 276 2285 5785 22045412201992 2550 prf: 2513410A Thermococcus litoralis malP 36.1 67.4 814maltodextrin phosphorylase/ glycogen phosphorylase 2286 5786 22054902204591 900 sp: YFIE_BACSU Bacillus subtilis 168 yfiE 33.9 66.4 295hypothetical protein 2287 5787 2208249 2207302 948 sp: LGT_STAAUStaphylococcus aureus FDA 485 31.4 65.5 264 prolipoproteindiacylglyceryl lgt transferase 2288 5788 2209167 2208367 801 sp:TRPG_EMENI Emericella nidulans trpC 29.6 62.1 169indole-3-glycerol-phosphate synthase/anthranilate synthase component II2289 5789 2209888 2209232 657 pir: H70556 Mycobacterium tuberculosis29.4 58.8 228 hypothetical membrane protein H37Rv Rv1610 2290 57902210273 2209920 354 sp: HIS3_RHOSH Rhodobacter sphaeroides ATCC 52.879.8 89 phosphoribosyl-AMP cyclohydrolase 17023 hisl 2291 5791 22110462210273 774 sp: HIS6_CORG Corynebacterium glutamicum 97.3 97.7 258cyclase AS019 hisF 2292 5792 2211875 2211051 825 prf: 2419176BCorynebacterium glutamicum 94.0 94.0 241 inositol monophosphate AS019impA phosphatase 2293 5793 2212619 2211882 738 gp: AF051846_1Corynebacterium glutamicum 95.9 97.6 245 phosphoribosylformimino-5-AS019 hisA aminoimidazole carboxamide ribotide isomerase 2294 57942213273 2212641 633 gp: AF060558_1 Corynebacterium glutamicum 86.7 92.4210 glutamine amidotransferase AS019 hisH 2295 5795 2215586 2214321 1266sp: CMLR_STRLI Streptomyces lividans 66 cmlR 25.6 54.0 402chloramphenicol resistance protein or transmembrane transport protein2296 5796 2215863 2215639 225 2297 5797 2216474 2215869 606 sp:HIS7_STRCO Streptomyces coelicolor A3(2) 52.5 81.8 198imidazoleglycerol-phosphate hisB dehydratase 2298 5798 2217591 22164941098 sp: HIS8_STRCO Streptomyces coelicolor A3(2) 57.2 79.3 362histidinol-phosphate hisC aminotransferase 2299 5799 2218925 22176001326 sp: HISX_MYCSM Mycobacterium smegmatis 63.8 85.7 439 histidinoldehydrogenase ATCC 607 hisD 2300 5800 2219159 2220358 1200 gp:SPBC215_13 Schizosaccharomyces pombe 27.2 54.4 342 serine-rich secretedprotein SPBC215.13 2301 5801 2221109 2220459 651 2302 5802 22216112221919 309 2303 5803 2221828 2221187 642 prf: 2321269A Leishmaniadonovani SAcP-1 29.4 59.7 211 histidine secretory acid phosphatase 23045804 2221958 2222518 561 pir: RPECR1 Escherichia coli plasmid RP1 28.960.8 204 tet repressor protein tetR 2305 5805 2222528 2225035 2508 prf:2307203B Sulfolobus acidocaldarius treX 47.4 75.5 722 glycogendebranching enzyme 2306 5806 2225149 2225949 801 pir: E70572Mycobacterium tuberculosis 50.0 76.0 258 hypothetical protein H37RvRv2622 2307 5807 2226763 2225990 774 gp: SC2G5_27 Streptomycescoelicolor A3(2) 29.9 55.2 268 oxidoreductase SC2G5.27c gip 2308 58082227779 2226769 1011 prf: 2503399A SinoRhizobium meliloti ldhA 35.0 60.9343 myo-inositol 2-dehydrogenase 2309 5809 2227906 2228901 996 sp:GALR_ECOLI Escherichia coli K12 galR 30.4 64.4 329 galactitolutilization operon repressor 2310 5810 2229896 2229099 798 sp:FHUC_BACSU Bacillus subtilis 168 fhuC 32.9 68.3 246 ferrichrometransport ATP-binding protein or ferrichrome ABC transporter 2311 58112230937 2229900 1038 prf: 2423441E Vibrio cholerae hutC 36.8 71.1 332hemin permease 2312 5812 2231294 2230947 348 pir: G70046 Bacillussubtilis 168 yvrC 30.1 68.0 103 iron-binding protein 2313 5813 22319322231339 594 pir: G70046 Bacillus subtilis 168 yvrC 34.6 67.6 182iron-binding protein 2314 5814 2232456 2232016 441 sp: YTFH_ECOLIEscherichia coli K12 ytfH 38.1 73.5 113 hypothetical protein 2315 58152232928 2234070 1143 gp: SCI8_12 Streptomyces coelicolor A3(2) 23.4 50.1355 DNA polymerase III epsilon chain SCI8.12 2316 5816 2234158 2234763606 2317 5817 2234852 2237284 2433 pir: S65769 Arthrobacter sp. Q36 treY42.0 68.6 814 maltooligosyl trehalose synthase 2318 5818 2237331 22383531023 gp: AE002006_4 Deinococcus radiodurans 27.6 52.8 322 hypotheticalprotein DR1631 2319 5819 2239092 2238694 399 2320 5820 2240042 2239845198 2321 5821 2240246 2240058 189 2322 5822 2240563 2239508 1056 23235823 2240681 2241724 1044 sp: LXA1_PHOLU Photorhabdus luminescens 20.554.4 375 alkanal monooxygenase alpha chain ATCC 29999 luxA 2324 58242242115 2241738 378 gp: SC7H2_5 Streptomyces coelicolor A3(2) 58.3 79.2120 hypothetical protein SC7H2.05 2325 5825 2242359 2242129 231 23265826 2243035 2244819 1785 pir: S65770 Arthrobacter sp. Q36 treZ 46.372.4 568 maltooligosyltrehalose trehalohydrolase 2327 5827 22430432242393 651 sp: YVYE_BACSU Bacillus subtilis 168 36.5 72.4 214hypothetical protein 2328 5828 2246171 2244864 1308 sp: THD1_CORGLCorynebacterium glutamicum 99.3 99.3 436 threonine dehydratase ATCC13032 ilvA 2329 5829 2246386 2246892 507 2330 5830 2246450 2246295 1562331 5831 2248208 2247006 1203 pir: S57636 Catharanthus roseus metE 22.749.6 415 Corynebacterium glutamicum AS019 2332 5832 2251939 2248358 3582prf: 2508371A Streptomyces coelicolor A3(2) 53.3 80.5 1183 DNApolymerase III dnaE 2333 5833 2252017 2252856 840 sp: RARD_ECOLIEscherichia coli K12 rarD 37.6 73.8 279 chloramphenicol sensitiveprotein 2334 5834 2253192 2253659 468 sp: HISJ_CAMJE Campylobacterjejuni DZ72 hisJ 21.5 55.7 149 histidine-binding protein precursor 23355835 2253725 2254642 918 pir: D69548 Archaeoglobus fulgidus AF2388 22.764.7 198 hypothetical membrane protein 2336 5836 2255558 2254683 876 sp:GS39_BACSU Bacillus subtilis 168 ydaD 48.2 80.0 280 short chaindehydrogenase or general stress protein 2337 5837 2257024 2255738 1287sp: DCDA_PSEAE Pseudomonas aeruginosa lysA 22.9 47.6 445 diaminopimelate(DAP) decarboxylase 2338 5838 2259312 2258362 951 sp: CYSM_ALCEUAlcaligenes eutrophus CH34 32.8 64.3 314 cysteine synthase cysM 23395839 2259999 2259421 579 2340 5840 2260931 2260002 930 sp: RLUD_ECOLIEscherichia coli K12 rluD 36.5 61.0 326 ribosomal large subunitpseudouridine synthase D 2341 5841 2261467 2260934 534 sp: LSPA_PSEFLPseudomonas fluorescens NCIB 33.8 61.7 154 lipoprotein signal peptidase10586 lspA 2342 5842 2261688 2262689 1002 2343 5843 2262850 2264499 1650pir: S67863 Streptomyces antibioticus oleB 36.4 64.0 550 oleandomycinresistance protein 2344 5844 2264996 2265298 303 2345 5845 22651082264509 600 prf: 2422382P Rhodococcus erythropolis orf17 36.7 57.6 158hypothetical protein 2346 5846 2265420 2266394 975 sp: ASPG_BACLIBacillus licheniformis 31.2 62.0 321 L-asparaginase 2347 5847 22682972266897 1401 sp: DINP_ECOLI Escherichia coli K12 dinP 31.8 60.7 371DNA-damage-inducible protein P 2348 5848 2269245 2268388 858 sp:YBIF_ECOLI Escherichia coli K12 ybiF 31.5 61.5 286 hypothetical membraneprotein 2349 5849 2270261 2269260 1002 gp: SCF51_6 Streptomycescoelicolor A3(2) 44.3 73.1 334 transcriptional regulator SCF51.06 23505850 2270304 2270435 132 2351 5851 2270884 2270258 627 gp: SCF51_5Streptomyces coelicolor A3(2) 42.0 67.0 212 hypothetical proteinSCF51.05 2352 5852 2274149 2270988 3162 sp: SYIC_YEAST Saccharomycescerevisiae 38.5 65.4 1066 isoleucyl-tRNA synthetase A364A YBL076C ILS12353 5853 2274688 2274473 216 2354 5854 2275861 2274767 1095 2355 58552276637 2276353 285 pir: F70578 Mycobacterium tuberculosis 46.3 73.2 82hypothetical membrane protein H37Rv Rv2146c 2356 5856 2277336 2276881456 gp: BLFTSZ_6 Brevibacterium lactofermentum 99.3 99.3 152hypothetical protein (putative YAK 1 orf6 protein) 2357 5857 22780782277416 663 sp: YFZ1_CORGL Corynebacterium glutamicum 97.7 99.6 221hypothetical protein 2358 5858 2278859 2278122 738 prf: 2420425CBrevibacterium lactofermentum 99.2 100.0 246 hypothetical protein yfih2359 5859 2279155 2279640 486 GP: AB028868_1 Mus musculus P4(21)n 39.051.0 117 hypothetical protein 2360 5860 2280215 2278890 1326 sp:FTSZ_BRELA Brevibacterium lactofermentum 98.6 98.6 442 cell divisionprotein ftsZ 2361 5861 2281135 2280470 666 gsp: W70502 Corynebacteriumglutamicum 99.6 100.0 222 cell division initiation protein or cell ftsQdivision protein 2362 5862 2282623 2281166 1458 gp: AB015023_1Corynebacterium glutamicum 99.4 99.8 486 UDP-N-acetylmuramate—alaninemurC ligase 2363 5863 2283776 2282661 1116 gp: BLA242646_3Brevibacterium lactofermentum 98.9 99.5 372 UDP-N-acetylglucosamine-N-ATCC 13869 murG acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenolN- acetylglucosamine pyrophosphoryl- undecaprenol N-acetylglucosamine2364 5864 2285431 2283782 1650 gp: BLA242646_3 Brevibacteriumlactofermentum 99.4 99.6 490 cell division protein ATCC 13869 ftsW 23655865 2285904 2285437 468 gp: BLA242646_1 Brevibacterium lactofermentum99.1 99.1 110 UDP-N-acetylmuramoylalanine-D- ATCC 13869 murD glutamateligase 2366 5866 2286272 2286655 384 2367 5867 2286499 2286831 333 23685868 2287959 2286862 1098 sp: MRAY_ECOLI Escherichia coli K12 mraY 38.663.8 365 phospho-n-acetylmuramoyl- pentapeptide 2369 5869 22895102287969 1542 sp: MURF_ECOLI Escherichia coli K12 murF 35.0 64.2 494UDP-N-acetylmuramoylalanyl-D- glutamyl-2,6-diaminoplmelate-D-alanyl-D-alanyl ligase 2370 5870 2291073 2289523 1551 sp: MURE_BACSUBacillus subtilis 168 murE 37.7 67.6 491 UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D- alanyl-D-alanyl ligase 2371 5871 22911972290973 225 GSP: Y33117 Brevibacterium lactofermentum 100.0 100.0 57penicillin binding protein ORF2 pbp 2372 5872 2293164 2291212 1953 pir:S54872 Pseudomonas aeruginosa pbpB 28.2 58.8 650 penicillin-bindingprotein 2373 5873 2294117 2293323 795 2374 5874 2295127 2294117 1011pir: A70581 Mycobacterium tuberculosis 55.1 79.3 323 hypotheticalprotein H37Rv Rv2165c 2375 5875 2295804 2295376 429 gp: MLCB268_11Mycobacterium leprae 72.0 88.8 143 hypothetical membrane proteinMLCB268.11c 2376 5876 2296898 2296512 387 pir: C70935 Mycobacteriumtuberculosis 39.4 69.3 137 hypothetical protein H37Rv Rv2169c 2377 58772297653 2297231 423 2378 5878 2297866 2298438 573 gp: MLCB268_13Mycobacterium leprae 36.3 65.3 190 hypothetical protein MLCB268.13 23795879 2299428 2298451 978 sp: METF_STRLI Streptomyces lividans 1326 42.670.6 303 5,10-methylenetetrahydrofolate metF reductase 2380 5880 22995242300636 1113 pir: S32168 Myxococcus xanthus DK1050 30.1 62.0 329dimethylallyltranstransferase ORF1 2381 5881 2300706 2302175 1470 gp:MLCB268_16 Mycobacterium leprae 35.7 69.6 484 hypothetical membraneprotein MLCB268.17 2382 5882 2302179 2302685 507 2383 5883 23026192302251 369 pir: A70936 Mycobacterium tuberculosis 43.2 68.8 125hypothetical protein H37Rv Rv2175c 2384 5884 2302833 2304980 2148 gp:AB019394_1 Streptomyces coelicolor A3(2) 34.2 62.4 684 eukaryotic-typeprotain kinase pkaF 2385 5885 2303690 2303040 651 2386 5886 23049832306218 1236 gp: MLCB268_21 Mycobacterium leprae 30.7 58.4 411hypothetical membrane protein MLCB268.23 2387 5887 2306314 2307621 1308pir: G70936 Mycobacterium tuberculosis 30.4 62.0 434 hypotheticalmembrane protein H37Rv Rv2181 2388 5888 2309082 2307697 1386 gp:AF260581_2 Amycolatopsis mediterranei 66.9 87.9 4623-deoxy-D-arabino-heptulosonate-7- phosphate synthase 2389 5889 23096762309173 504 gp: MLCB268_20 Mycobacterium leprae 58.4 77.7 166hypothetical protein MLCB268.21c 2390 5890 2309835 2312252 2418 pir:G70936 Mycobacterium tuberculosis 35.1 64.5 428 hypothetical membraneprotein H37Rv Rv2181 2391 5891 2312360 2313808 1449 sp: CSP1_CORGLCorynebacterium glutamicum 28.2 57.1 440 major secreted protein PS1protein (Brevibacterium flavum) ATCC precursor 17965 csp1 2392 58922313833 2314036 204 2393 5893 2314092 2313916 177 2394 5894 23154232314236 1188 gp: AF096280_3 Corynebacterium glutamicum 100.0 100.0 249hypothetical membrane protein ATCC 13032 2395 5895 2316412 2315678 735gp: AF096280_2 Corynebacterium glutamicum 100.0 100.0 245acyltransferase ATCC 13032 2396 5896 2318775 2317633 1143 gp: SC6G10_5Streptomyces coelicolor A3(2) 50.1 75.7 383 glycosyl transferaseSC6G10.05c 2397 5897 2319850 2318804 1047 sp: P60_LISIV Listeriaivanovii iap 26.4 60.8 296 protein P60 precursor (invasion-associated-protein) 2398 5898 2320594 2319968 627 sp: P60_LISGR Listeriagrayi iap 33.0 61.3 191 protein P60 precursor (invasion-associated-protein) 2399 5899 2323073 2321472 1602 prf: 2503462KHeliobacillus mobilis petB 34.3 64.7 201 ubiquinol-cytochrome creductase cytochrome b subunit 2400 5900 2323759 2323088 672 gp:AF107888_1 Streptomyces lividans qcrA 37.9 57.1 203 ubiquinol-cytochromec reductase iron-sulfur subunit (Rieske [eFe-2S] iron-sulfur proteincyoB 2401 5901 2325195 2324311 885 sp: Y005_MYCTU Mycobacteriumtuberculosis 58.6 83.1 278 ubiquinol-cytochrome c reductase H37Rv Rv2194qcrC cytochrome c 2402 5902 2325887 2325273 615 sp: COX3_SYNVUSynechococcus vulcanus 36.7 70.7 188 cytochrome c oxidase subunit III2403 5903 2326273 2326121 153 2404 5904 2326900 2326472 429 sp:Y00A_MYCTU Mycobacterium tuberculosis 38.6 71.0 145 hypotheticalmembrane protein H37Rv Rv2199c 2405 5905 2327997 2326921 1077 sp:COX2_RHOSH Rhodobacter sphaeroides ctaC 28.7 53.9 317 cytochrome coxidase subunit II 2406 5906 2328516 2330435 1920 gp: AB029550_1Corynebacterium glutamicum 99.7 99.8 640 glutamine-dependent KY9611 ltsAamidotransferase or asparagine synthetase (lysozyme insensitivityprotein) 2407 5907 2330927 2330586 342 gp: AB029550_2 Corynebacteriumglutamicum 100.0 100.0 114 hypothetical protein KY9611 orf1 2408 59082331200 2331967 768 gp: MLCB22_2 Mycobacterium leprae 35.0 60.2 246hypothetical membrane protein MLCB22.07 2409 5909 2331974 2332495 522pir: S52220 Rhodobacter capsulatus cobP 43.0 64.0 172 cobinamide kinase2410 5910 2332512 2333600 1089 sp: COBU_PSEDE Pseudomonas denitrificans37.8 66.9 341 nicotinate-nucleotide— cobU dimethylbenzimidazolephosphoribosyltransferase 2411 5911 2333615 2334535 921 sp: COBV_PSEDEPseudomonas denitrificans cobV 25.3 49.8 305 cobalamin (5′-phosphate)synthase 2412 5912 2334717 2334481 237 2413 5913 2335741 2335028 714prf: 2414335A Streptomyces clavuligerus car 38.6 68.5 241clavulanate-9-aldehyde reductase 2414 5914 2337051 2335915 1137 sp:ILVE_MYCTU Mus musculus BCAT1 40.1 70.3 364 branched-chain amino acidaminotransferase 2415 5915 2337235 2338734 1500 gp: PPU010261_1Pseudomonas putida ATCC 36.3 65.9 493 leucyl aminopeptidase 12633 pepA2416 5916 2339140 2338748 393 prf: 2110282A Saccharopolyspora erythraea40.2 67.0 97 hypothetical protein ORF1 2417 5917 2339269 2341293 2025gp: AF047034_2 Streptomyces seoulensis pdhB 48.9 68.5 691dihydrolipoamide acetyltransferase 2418 5918 2340804 2339440 1365 24195919 2341412 2342164 753 gp: AB020975_1 Arabidopsis thaliana 36.7 65.7210 lipoyltransferase 2420 5920 2342304 2343347 1044 sp: LIPA_PELCAPelobacter carbinolicus GRA BD1 44.6 70.9 285 lipoic acid synthetaselipA 2421 5921 2343479 2344258 780 sp: Y00U_MYCTU Mycobacteriumtuberculosis 45.5 76.7 257 hypothetical membrane protein H37Rv Rv22192422 5922 2344431 2346047 1617 sp: YIDE_ECOLI Escherichia coli K12 yidE32.9 67.8 559 hypothetical membrane protein 2423 5923 2347491 23462891203 gp: AF189147_1 Corynebacterium glutamicum 100.0 100.0 401transposase (ISCg2) ATCC 13032 tnp 2424 5924 2347505 2347804 300 24255925 2348548 2348078 471 gp: SC5F7_34 Streptomyces coelicolor A3(2) 41.463.7 157 hypothetical membrane protein SC5F7.04c 2426 5926 23506202350408 213 2427 5927 2351022 2351996 975 31.0 44.0 145 mutator mutTdomain protein 2428 5928 2351310 2350912 399 pir: B72308 Thermotogamaritima MSB8 36.7 65.6 128 hypothetical protein TM1010 2429 59292351909 2351310 600 2430 5930 2351980 2352828 849 sp: LUXA_VIBHA Vibrioharveyi luxA 25.0 60.9 220 alkanal monooxygenase alpha chain (bacterialluciferase alpha chain) 2431 5931 2352833 2353225 393 pir: A72404Thermotoga maritima MSB8 40.5 73.0 111 protein synthesis inhibitorTM0215 (translation initiation inhibitor) 2432 5932 2355156 2355398 2432433 5933 2355440 2355180 261 2434 5934 2355521 2356843 1323 prf:2203345H Escherichia coli hpaX 21.9 53.4 433 4-hydroxyphenylacetatepermease 2435 5935 2356794 2357354 561 gp: SCGD3_10 Streptomycescoelicolor A3(2) 42.4 72.8 158 transmembrane transport protein SCGD3.10c2436 5936 2357264 2357707 444 gp: SCGD3_10 Streptomyces coelicolor A3(2)31.4 66.1 118 transmembrane transport protein SCGD3.10c 2437 59372357484 2357290 195 2438 5938 2357726 2358130 405 2439 5939 23586952358153 543 2440 5940 2359416 2358772 645 sp: HMUO_CORDI Corynebacteriumdiphtheriae C7 57.9 78.0 214 heme oxygenase hmuO 2441 5941 23627482359614 3135 gp: SCY17736_4 Streptomyces coelicolor A3(2) 43.4 67.0 809glutamate-ammonia-ligase glnE adenylyltransferase 2442 5942 23641552362818 1338 sp: GLNA_THEMA Thermotoga maritima MSB8 43.5 73.0 441glutamine synthetase glnA 2443 5943 2364352 2365455 1104 gp: SCE9_39Streptomyces coelicolor A3(2) 26.8 54.1 392 hypothetical proteinSCE9.39c 2444 5944 2365587 2367413 1827 sp: Y017_MYCTU Mycobacteriumtuberculosis 33.4 58.2 601 hypothetical protein H37Rv Rv2226 2445 59452367652 2367473 180 gp: SCC75A_11 Streptomyces coelicolor A3(2) 38.955.6 54 hypothetical protein SCC75A.11c. 2446 5946 2367791 2369083 1293sp: GAL1_HUMAN Homo sapiens galK1 24.9 53.7 374 galactokinase 2447 59472370381 2369116 1266 gp: AF174645_1 Brucella abortus vacB 27.1 54.5 358virulence-associated protein 2448 5948 2370423 2370908 486 2449 59492372557 2371412 1146 sp: Y019_MYCTU Mycobacterium tuberculosis 54.7 75.1382 bifunctional protein (ribonuclease H H37Rv Rv2228c andphosphoglycerate mutase) 2450 5950 2372561 2373289 729 2451 5951 23732892372573 717 sp: Y01A_MYCTU Mycobacterium tuberculosis 26.5 58.6 249hypothetical protein H37Rv Rv2229c 2452 5952 2374462 2373323 1140 sp:Y01B_MYCTU Mycobacterium tuberculosis 49.2 76.2 378 hypothetical proteinH37Rv Rv2230c 2453 5953 2374544 2375197 654 sp: GPH_ECOLI Escherichiacoli K12 gph 26.0 54.4 204 phosphoglycolate phosphatase 2454 59542375214 2375684 471 sp: PTPA_STRCO Streptomyces coelicolor A3(2) 46.263.5 156 low molecular weight protein- SCQ11.04c ptpAtyrosine-phosphatase 2455 5955 2375767 2376720 954 sp: Y01G_MYCTUMycobacterium tuberculosis 40.9 65.5 281 hypothetical protein H37RvRv2235 2456 5956 2377390 2376998 393 sp: YI21_BURCE Burkholderia cepacia32.6 56.6 129 insertion element (IS402) 2457 5957 2377726 2377484 2432458 5958 2377899 2378276 378 gp: SC8F4_22 Streptomyces coelicolor A3(2)30.4 57.8 135 transcriptional regulator SC8F4.22c 2459 5959 23782922378489 198 2460 5960 2379312 2378884 429 sp: Y01K_MYCTU Mycobacteriumtuberculosis 55.2 77.6 134 hypothetical protein H37Rv Rv2239c 2461 59612379426 2379770 345 2462 5962 2380033 2382744 2712 gp: AF047034_4Streptomyces seoulensis pdhA 55.9 78.9 910 pyruvate dehydrogenasecomponent 2463 5963 2382240 2380765 1476 2464 5964 2383615 2382827 789sp: GLNQ_ECOLI Escherichia coli K12 glnQ 33.7 62.8 261 ABC transporteror glutamine transport ATP-binding protein 2465 5965 2384464 2385426 9632466 5966 2384509 2383622 888 sp: RBSC_BACSU Bacillus subtilis 168 rbsC25.4 58.7 283 ribose transport system permease protein 2467 5967 23854472384509 939 pir: H71693 Rickettsia prowazekii Madrid E 26.2 62.9 286hypothetical protein RP367 2468 5968 2385771 2386580 810 sp: CBPA_DICDIDictyostelium discoideum AX2 41.6 55.2 125 calcium binding protein cbpA2469 5969 2386284 2385913 372 2470 5970 2387627 2386614 1014 gp:SC6G4_24 Streptomyces coelicolor A3(2) 29.6 55.7 352 lipase or hydrolaseSC6G4.24 2471 5971 2387667 2387957 291 sp: ACP_MYXXA Myxococcus xanthusATCC 42.7 80.0 75 acyl carier protein 25232 acpP 2472 5972 23879972388821 825 sp: NAGD_ECOLI Escherichia coli K12 nagD 43.9 75.5 253N-acetylglucosamine-6-phosphate deacetylase 2473 5973 2388838 23898691032 gp: AE001968_4 Deinococcus radiodurans 33.6 65.7 289 hypotheticalprotein DR1192 2474 5974 2390904 2390434 471 2475 5975 2392008 2391184825 gp: SC4A7_8 Streptomyces coelicolor A3(2) 52.4 75.3 271 hypotheticalprotein SC4A7.08 2476 5976 2392566 2392075 492 2477 5977 2393349 2392579771 2478 5978 2393425 2393970 546 2479 5979 2394437 2393973 465 24805980 2394594 2394935 342 2481 5981 2395204 2396763 1560 sp: PPBD_BACSUBacillus subtilis 168 phoD 34.2 64.7 530 alkaline phosphatase Dprecursor 2482 5982 2395986 2395273 714 2483 5983 2397264 2399099 1836gp: SCI51_17 Streptomyces coelicolor A3(2) 44.4 73.1 594 hypotheticalprotein SCI51.17 2484 5984 2399158 2399397 240 pir: G70661 Mycobacteriumtuberculosis 41.2 72.1 68 hypothetical protein H37Rv Rv2342 2485 59852400342 2399668 675 2486 5986 2401303 2399405 1899 prf: 2413330BMycobacterium smegmatis 59.1 82.9 633 DNA primase dnaG 2487 5987 24013732401834 462 gp: XXU39467_1 Streptomyces aureofaciens BMK 49.0 67.4 98ribonuclease Sa 2488 5988 2401838 2402080 243 2489 5989 2403165 2402530636 2490 5990 2404012 2402144 1869 gp: AF058788_1 Mycobacteriumsmegmatis 59.1 82.2 636 L-glutamine: D-fructose-6-phosphate mc2155 glmSamidotransferase 2491 5991 2404523 2404846 324 2492 5992 2405671 24068221152 2493 5993 2406258 2404987 1272 prf: 2413330A Mycobacteriumsmegmatis dgt 54.6 76.3 414 deoxyguanosinetriphosphatetriphosphohydrolase 2494 5994 2406936 2406262 675 gp: NMA1Z2491_235Neisseria meningitidis NMA0251 30.4 59.7 171 hypothetical protein 24955995 2406993 2409029 2037 pir: B70662 Mycobacterium tuberculosis 31.163.6 692 hypothetical protein H37Rv Rv2345 2496 5996 2410264 2409779 486gp: AE003565_26 Drosophila melanogaster 24.6 54.4 138 hypotheticalprotein CG10592 2497 5997 2410861 2410280 582 2498 5998 2412338 24109561383 pir: S58522 Thermus aquaticus HB8 46.1 69.9 508 glycyl-tRNAsynthetase 2499 5999 2412580 2412948 369 pir: E70585 Mycobacteriumtuberculosis 49.4 73.0 89 bacterial regulatory protein, arsR H37RvRv2358 furB family 2500 6000 2412992 2413423 432 sp: FUR_ECOLIEscherichia coli K12 fur 34.9 70.5 132 ferric uptake regulation protein2501 6001 2413568 2415118 1551 pir: A70539 Mycobacterium tuberculosis24.8 46.7 529 hypothetical protein (conserved in H37Rv Rv1128c C.glutamicum?) 2502 6002 2416089 2415298 792 gp: AF162938_1 Streptomycescoelicolor A3(2) 40.6 67.0 224 hypothetical membrane protein h3u 25036003 2417099 2416371 729 sp: UPPS_MICLU Micrococcus luteus B-P 26 uppS43.4 71.2 233 undecaprenyl diphosphate synthase 2504 6004 24179472417222 726 pir: A70586 Mycobacterium tuberculosis 45.7 74.3 245hypothetical protein H37Rv Rv2362c 2505 6005 2418883 2417969 915 gp:AF072811_1 Streptococcus pneumoniae era 39.5 70.3 296 Era-likeGTP-binding protein 2506 6006 2420309 2418990 1320 sp: Y1DE_MYCTUMycobacterium tuberculosis 52.8 82.4 432 hypothetical membrane proteinH37Rv Rv2366 2507 6007 2420900 2420313 588 sp: YN67_MYCTU Mycobacteriumtuberculosis 65.0 86.0 157 hypothetical protein H37Rv Rv2367c 2508 60082420973 2421236 264 GSP: Y75650 Neisseria meningitidis 45.0 50.0 85Neisserial polypeptides predicted to be useful antigens for vaccines anddiagnostics 2509 6009 2421949 2420900 1050 sp: PHOL_MYCTU Mycobacteriumtuberculosis 61.1 84.6 344 phosphate starvation inducible H37Rv Rv2368cphoH protein 2510 6010 2422697 2421975 723 gp: SCC77_19 Streptomycescoelicolor A3(2) 44.0 75.4 248 hypothetical protein SCC77.19c. 2511 60112422850 2423791 942 2512 6012 2423845 2422700 1146 prf: 2421342BStreptomyces albus dnaJ2 47.1 77.4 380 heat shock protein dnaJ 2513 60132424937 2423915 1023 prf: 2421342A Streptomyces albus hrcA 48.2 79.6 334heat-inducible transcriptional repressor (groEL repressor) 2514 60142425954 2424965 990 prf: 2318256A Bacillus stearothermophilus 33.1 64.1320 oxygen-independent hemN coproporphyrinogen III oxidase 2515 60152426181 2426699 519 sp: AGA1_YEAST Saccharomyces cerevisiae 36.6 64.9134 agglutinin attachment subunit YNR044W AGA1 precursor 2516 60162427468 2426776 693 2517 6017 2428184 2427807 378 2518 6018 24300282428184 1845 gp: SC6G10_4 Streptomyces coelicolor A3(2) 48.0 75.1 611long-chain-fatty-acid—CoA ligase SC6G10.04 2519 6019 2430296 24324132118 sp: MALQ_ECOLI Escherichia coli K12 malQ 28.3 55.4 7384-alpha-glucanotransferase 2520 6020 2432508 2434370 1863 gp: AB005752_1Lactobacillus brevis plasmid 29.5 64.4 604 ABC transporter,Hop-Resistance horA protein 2521 6021 2433868 2433614 255 GSP: Y74827Neisseria gonorrhoeae 44.0 51.0 68 Neisserial polypeptides predicted tobe useful antigens for vaccines and diagnostics 2522 6022 24342072433875 333 GSP: Y74829 Neisseria meningitidis 47.0 53.0 107polypeptides predicted to be useful antigens for vaccines anddiagnostics 2523 6023 2434619 2434440 180 2524 6024 2434776 2434573 2042525 6025 2436838 2434805 2034 sp: DCP_SALTY Salmonella typhimurium dcp40.3 68.3 690 peptidyl-dipeptidase 2526 6026 2436871 2438049 1179 gp:AF064523_1 Anisopteromalus calandrae 24.1 45.7 453 carboxylesterase 25276027 2438113 2439906 1794 pir: G70983 Mycobacterium tuberculosis 65.284.9 594 glycosyl hydrolase or trehalose H37Rv Rv0126 synthase 2528 60282439906 2440994 1089 pir: H70983 Mycobacterium tuberculosis 32.1 58.8449 hypothetical protein H37Rv Rv0127 2529 6029 2441589 2441005 585 pir:T07979 Chlamydomonas reinhardtii ipi1 31.8 57.7 189isopentenyl-diphosphate Delta- isomerase 2530 6030 2441669 2441890 2222531 6031 2442355 2442792 438 2532 6032 2443356 2441602 1755 2533 60332444015 2443356 660 2534 6034 2444551 2444033 519 2535 6035 24447352445709 975 gp: CORCSLYS_1 Corynebacterium glutamicum 99.4 100.0 325beta C-S lyase (degradation of ATCC 13032 aecD aminoethylcysteine) 25366036 2445716 2446993 1278 sp: BRNQ_CORGL Corynebacterium glutamicum 99.8100.0 426 branched-chain amino acid transport ATCC 13032 brnQ systemcarrier protein (isoleucine uptake) 2537 6037 2447021 2447998 978 sp:LUXA_VIBHA Vibrio harveyi luxA 21.6 49.0 343 alkanal monooxygenase alphachain 2538 6038 2450844 2450323 522 2539 6039 2451785 2450859 927 gp:AF155772_2 SinoRhizobium meliloti mdcF 25.9 60.5 324 malonatetransporter 2540 6040 2454637 2451794 2844 sp: GLCD_ECOLI Escherichiacoli K12 glcD 27.7 55.1 483 glycolate oxidase subunit 2541 6041 24547252455435 711 sp: YDFH_ECOLI Escherichia coli K12 ydfH 25.6 65.0 203transcriptional regulator 2542 6042 2455733 2455452 282 2543 60432457066 2455720 1347 sp: YGIK_SALTY Salmonella typhimurium ygiK 22.557.6 467 hypothetical protein 2544 6044 2457759 2457337 423 2545 60452457863 2459371 1509 sp: HBPA_HAEIN Haemophilus influenzae Rd 27.5 55.5546 heme-binding protein A precursor HI0853 hbpA (hemin-bindinglipoprotein) 2546 6046 2459371 2460336 966 sp: APPB_BACSU Bacillussubtilis 168 appB 40.0 73.3 315 oligopeptide ABC transporter (permease)2547 6047 2460340 2461167 828 sp: DPPC_ECOLI Escherichia coli K12 dppC43.2 74.5 271 dipeptide transport system permease protein 2548 60482461163 2462599 1437 prf: 2306258MR Escherichia coli K12 oppD 37.4 66.4372 oligopeptide transport ATP-binding protein 2549 6049 2462049 2461543507 PIR: G72536 Aeropyrum pernix K1 APE1580 35.0 44.0 106 hypotheticalprotein 2550 6050 2463150 2462602 549 pir: D70367 Aquifex aeolicus VF5aq_768 29.3 58.0 157 hypothetical protein 2551 6051 2463241 2464143 903prf: 2514301A Rhizobium etli rbsK 41.0 65.0 300 ribose kinase 2552 60522464344 2465768 1425 gp: SCM2_16 Streptomyces coelicolor A3(2) 39.9 64.6466 hypothetical membrane protein SCM2.16c 2553 6053 2465767 2465465 3032554 6054 2467009 2466038 972 sp: NTCI_HUMAN Homo sapiens 31.3 61.6 284sodium-dependent transporter or odium Bile acid symporter family 25556055 2467077 2467922 846 gp: AF195243_1 Chlamydomonas reinhardtii 28.551.2 295 apospory-associated protein C 2556 6056 2470313 2470678 3662557 6057 2472250 2472819 570 sp: THIX_CORGL Corynebacterium glutamicum100.0 100.0 133 thiamine biosynthesis protein x ATCC 13032 thiX 25586058 2473480 2472893 588 sp: VG66_BPMD Mycobacteriophage D29 66 42.665.5 197 hypothetical protein 2559 6059 2473653 2475542 1890 sp:BETP_CORGL Corynebacterium glutamicum 39.8 71.7 601 glycine betainetransporter ATCC 13032 betP 2560 6060 2476497 2477492 996 2561 60612477644 2479251 1608 2562 6062 2479379 2479762 384 2563 6063 24812082479898 1311 prf: 2320266C Rhodobacter capsulatus dctM 34.6 71.9 448large integral C4-dicarboxylate membrane transport protein 2564 60642481692 2481213 480 gp: AF186091_1 Klebsiella pneumoniae dctQ 33.9 73.7118 small integral C4-dicarboxylate membrane transport protein 2565 60652482480 2481734 747 sp: DCTP_RHOCA Rhodobacter capsulatus B10 28.2 59.0227 C4-dicarboxylate-binding dctP periplasmic protein precursor 25666066 2483845 2484087 243 PRF: 1806416A Lycopersicon esculentum 63.0 73.046 extensin I (tomato) 2567 6067 2484392 2482548 1845 sp: LEPA_BACSUBacillus subtilis 168 lepA 58.7 83.6 603 GTP-binding protein 2568 60682484661 2485269 609 pir: H70683 Mycobacterium tuberculosis 41.6 69.7 185hypothetical protein H37Rv Rv2405 2569 6069 2485473 2485733 261 sp:RS20_ECOLI Escherichia coli K12 rpsT 48.2 72.9 85 30S ribosomal proteinS20 2570 6070 2486469 2485801 669 sp: RHTC_ECOLI Escherichia coli K12rhtC 30.0 67.1 210 thrreonine efflux protein 2571 6071 2486881 2486477405 gp: SC6D7_25 Streptomyces coelicolor A3(2) 61.2 80.6 129ankyrin-like protein SC6D7.25. 2572 6072 2487884 2486910 975 pir: H70684Mycobacterium tuberculosis 46.0 74.1 313 hypothetical protein H37RvRv2413c 2573 6073 2489450 2487912 1539 sp: CME3_BACSU Bacillus subtilis168 comEC 21.4 49.7 527 late competence operon required for DNA bindingand uptake 2574 6074 2490154 2489573 582 sp: CME1_BACSU Bacillussubtilis 168 comEA 30.8 63.6 195 late competence operon required for DNAbinding and uptake 2575 6075 2490911 2491732 822 2576 6076 24911112490290 822 gp: SCC123_7 Streptomyces coelicolor A3(2) 34.8 66.3 273hypothetical protein SCC123.07c. 2577 6077 2491858 2491151 708 pir:F70685 Mycobacterium tuberculosis 46.8 66.4 235 phosphoglycerate mutaseH37Rv Rv2419c 2578 6078 2492343 2491873 471 pir: G70685 Mycobacteriumtuberculosis 55.6 86.3 117 hypothetical protein H37Rv Rv2420c 2579 60792493178 2492501 678 gp: SCC123_17 Streptomyces coelicolor A3(2) 68.085.3 197 hypothetical protein SCC123.17c. 2580 6080 2494237 2493215 10232581 6081 2495634 2494339 1296 sp: PROA_CORGL Corynebacterium glutamicum99.1 99.8 432 gamma-glutamyl phosphate ATCC 17965 proA reductase orglutamate-5- semialdehyde dehydrogenase 2582 6082 2496607 2495696 912sp: YPRA_CORGL Corynebacterium glutamicum 99.3 100.0 304 D-isomerspecific 2-hydroxyacid ATCC 17965 unkdh dehydrogenase 2583 6083 24968032497513 711 2584 6084 2499511 2498009 1503 gp: D87915_1 Streptomycescoelicolor A3(2) 58.9 78.2 487 GTP-binding protein obg 2585 6085 24997832501669 1887 sp: PBUX_BACSU Bacillus subtilis 168 pbuX 39.1 77.3 422xanthine permease 2586 6086 2502577 2501735 843 pir: I40838Corynebacterium sp. ATCC 61.2 81.9 276 2,5-diketo-D-gluconic acidreductase 31090 2587 6087 2502735 2503355 621 2588 6088 2503870 2504265396 2589 6089 2504247 2503984 264 sp: RL27_STRGR Streptomyces griseusIFO13189 80.3 92.6 81 50S ribosomal protein L27 rpmA 2590 6090 25046022504300 303 prf: 2304263A Streptomyces griseus IFO13189 56.4 82.2 10150S ribosomal protein L21 obg 2591 6091 2507098 2504831 2268 sp:RNE_ECOLI Escherichia coli K12 rne 30.1 56.6 886 ribonuclease E 25926092 2507115 2507663 549 2593 6093 2507138 2507710 573 2594 6094 25080942508840 747 2595 6095 2508922 2509530 609 gp: SCF76_8 Streptomycescoelicolor A3(2) 61.0 82.6 195 hypothetical protein SCF76.08c 2596 60962510830 2509523 1308 plr: S43613 Corynebacterium glutamicum 99.1 100.0436 transposase (insertion sequence ATCC 31831 IS31831) 2597 60972511046 2511423 378 gp: SCF76_8 Streptomyces coelicolor A3(2) 51.3 76.9117 hypothetical protein SCF76.08c. 2598 6098 2511427 2511876 450 gp:SCF76_9 Streptomyces coelicolor A3(2) 37.8 67.8 143 hypothetical proteinSCF76.09 2599 6099 2512356 2511949 408 gp: AF069544_1 Mycobacteriumsmegmatis ndk 70.9 89.6 134 nucleoside diphosphate kinase 2600 61002512768 2512409 360 2601 6101 2512803 2513144 342 gp: AE002024_10Deinococcus radiodurans R1 34.8 67.4 92 hypothetical protein DR1844 26026102 2513618 2513154 465 pir: H70515 Mycobacterium tuberculosis 36.664.3 112 hypothetical protein H37Rv Rv1883c 2603 6103 2514114 2513692423 pir: E70863 Mycobacterium tuberculosis 33.9 68.6 118 hypotheticalprotein H37Rv Rv2446c 2604 6104 2515487 2514114 1374 prf: 2410252BStreptomyces coelicolor A3(2) 55.4 79.6 451 folyl-polyglutamatesynthetase folC 2605 6105 2515662 2516273 612 2606 6106 2516243 2516956714 2607 6107 2517089 2517751 663 2608 6108 2518336 2515637 2700 sp:SYV_BACSU Bacillus subtilis 168 balS 45.5 72.1 915 valyl-tRNA synthetase2609 6109 2519972 2518398 1575 pir: A38447 Bacillus subtilis 168 oppA24.2 58.5 521 oligopeptide ABC transport system substrate-bindingprotein 2610 6110 2520209 2521660 1452 sp: DNAK_BACSU Bacillus subtilis168 dnaK 26.2 54.9 508 heat shock protein dnaK 2611 6111 2522251 2521667585 gp: ECU89166_1 Eikenella corrodens ATCC 42.9 71.2 170 lysinedecarboxylase 23824 2612 6112 2523248 2522265 984 sp: MDH_THEFL Thermusaquaticus ATCC 33923 56.4 76.5 319 malate dehydrogenase mdh 2613 61132523561 2524337 777 gp: SC4A10_33 Streptomyces coelicolor A3(2) 24.656.5 207 transcriptional regulator SC4A10.33 2614 6114 2524915 2524340576 gp: AF065442_1 Vibrio cholerae aphA 26.0 51.4 208 hypotheticalprotein 2615 6115 2525099 2526226 1128 prf: 2513416F Acinetobacter sp.vanA 39.5 68.6 357 vanillate demethylase (oxygenase) 2616 6116 25262332527207 975 gp: FSU12290_2 Sphingomonas flava ATCC 32.8 59.2 338pentachlorophenol 4- 39723 pcpD monooxygenase reductase 2617 61172527135 2528559 1425 prf: 2513416G Acinetobacter sp. vanK 40.8 76.8 444transport protein 2618 6118 2529480 2528551 930 gp: KPU95087_7Klebsiella pneumoniae mdcF 28.0 58.4 286 malonate transporter 2619 61192530761 2529484 1278 prf: 2303274A Bacillus subtilis clpX 59.8 85.8 430class-III heat-shock protein or ATP- dependent protease 2620 61202530891 2531976 1086 gp: SCF55_28 Streptomyces coelicolor A3(2) 45.673.0 366 hypothetical protein SCF55.28c 2621 6121 2532601 2531969 633gp: AF109386_2 Streptomyces sp. 2065 pcaJ 63.3 85.7 210 succinyl CoA:3-oxoadipate CoA transferase beta subunit 2622 6122 2533353 2532604 750gp: AF109386_1 Streptomyces sp. 2065 pcal 60.2 84.5 251 succinyl CoA:3-oxoadipate CoA transferase alpha subunit 2623 6123 2533391 2534182 792prf: 2408324F Rhodococcus opacus 1CP pcaR 58.2 82.5 251 protocatechuatecatabolic protein 2624 6124 2534201 2535424 1224 prf: 2411305D Ralstoniaeutropha bktB 44.8 71.9 406 beta-ketothiolase 2625 6125 2535168 2534257912 2626 6126 2535430 2536182 753 prf: 2408324E Rhodococcus opacus pcaL50.8 76.6 256 3-oxoadipate enol-lactone hydrolase and4-carboxymuconolactone decarboxylase 2627 6127 2536196 2538256 2061 gp:SCM1_10 Streptomyces coelicolor A3(2) 23.6 43.0 825 transcriptionalregulator SCM1.10 2628 6128 2538613 2538248 366 prf: 2408324ERhodococcus opacus pcaL 78.3 89.6 115 3-oxoadipate enol-lactonehydrolase and 4-carboxymuconolactone decarboxylase 2629 6129 25395532540230 678 2630 6130 2539731 2538616 1116 prf: 2408324D Rhodococcusopacus pcaB 39.8 63.4 437 3-carboxy-cis, cis-muconate cycloisomerase2631 6131 2540320 2539709 612 prf: 2408324C Rhodococcus opacus pcaG 49.570.6 214 protocatechuate dioxygenase alpha subunit 2632 6132 25410242540335 690 prf: 2408324B Rhodococcus opacus pcaH 74.7 91.2 217protocatechuate dioxygenase beta subunit 2633 6133 2542350 2541187 1164pir: G70506 Mycobacterium tuberculosis 26.4 48.7 273 hypotheticalprotein H37Rv Rv0336 2634 6134 2542802 2542512 291 prf: 2515333BMycobacterium tuberculosis 54.4 81.5 92 muconolactone isomerase catC2635 6135 2543043 2543813 771 2636 6136 2543936 2542818 1119 sp:CATB_RHOOP Rhodococcus opacus 1CP catB 60.8 84.7 372 muconatecycloisomerase 2637 6137 2544262 2544867 606 2638 6138 2544876 2544022855 prf: 2503218A Rhodococcus rhodochrous catA 72.3 88.4 285 catechol1,2-dioxygenase 2639 6139 2545068 2544928 141 2640 6140 2545315 25467841470 gp: AF134348_1 Pseudomonas putida plasmid 62.2 85.6 437 toluate 1,2dioxygenase subunit pDK1 xylX 2641 6141 2546827 2547318 492 gp:AF134348_2 Pseudomonas putida plasmid 60.3 83.2 161 toluate 1,2dioxygenase subunit pDK1 xylY 2642 6142 2547333 2548868 1536 gp:AF134348_3 Pseudomonas putida plasmid 51.5 81.0 342 toluate 1,2dioxygenase subunit pDK1 xylZ 2643 6143 2548868 2549695 828 gp:AF134348_4 Pseudomonas putida plasmid 30.7 61.4 2771,2-dihydroxycyclohexa-3,5-diene pDK1 xylL carboxylate dehydrogenase2644 6144 2549771 2552455 2685 gp: REU95170_1 Rhodococcus erythropolisthcG 23.3 48.6 979 regulator of LuxR family with ATP- binding site 26456145 2552563 2553942 1380 sp: PCAK_ACICA Acinetobacter calcoaceticus31.3 64.4 435 transmembrane transport protein or pcaK 4-hydroxybenzoatetransporter 2646 6146 2554026 2555267 1242 sp: BENE_ACICA Acinetobactercalcoaceticus 29.9 66.2 388 benzoate membrane transport benE protein2647 6147 2555940 2555317 624 gp: AF071885_2 Streptomyces coelicolorM145 69.5 88.3 197 ATP-dependent Clp protease clpP2 proteolytic subunit2 2648 6148 2556580 2555978 603 gp: AF071885_1 Streptomyces coelicolorM145 62.1 85.9 198 ATP-dependent Clp protease clpP1 proteolytic subunit1 2649 6149 2556599 2556748 150 gp: SIS243537_4 Sulfolobus islandicusORF154 42.9 71.4 42 hypothetical protein 2650 6150 2558106 2556760 1347sp: TIG_BACSU Bacillus subtilis 168 tig 32.1 66.4 417 trigger factor(prolyl isomerase) (chaperone protein) 2651 6151 2558609 2559103 495 gp:SCD25_17 Streptomyces coelicolor A3(2) 32.5 63.1 160 hypotheticalprotein SCD25.17 2652 6152 2559157 2560131 975 sp: PBP4_NOCLA Nocardialactamdurans LC411 25.3 50.9 336 penicillin-binding protein pbp 26536153 2560131 2560586 456 prf: 2301342A Mus musculus Moa1 27.8 58.3 115hypothetical protein 2654 6154 2561115 2561363 249 2655 6155 25619202561483 438 prf: 2513302C Corynebacterium striatum ORF1 54.2 73.2 142transposase 2656 6156 2562093 2562242 150 2657 6157 2562115 2561990 126prf: 2513302C Corynebacterium striatum ORF1 57.1 82.9 35 hypotheticalprotein 2658 6158 2562341 2562078 264 prf: 2513302C Corynebacteriumstriatum ORF1 50.7 78.7 75 transposase 2659 6159 2562776 2562387 3902660 6160 2562963 2563847 885 2661 6161 2564402 2563932 471 sp:LACB_STAAU Staphylococcus aureus NCTC 40.0 71.4 140galactose-6-phosphate isomerase 8325-4 lacB 2662 6162 2565245 2564550696 sp: YAMY_BACAD Bacillus acidopullulyticus ORF2 26.2 58.1 248hypothetical protein 2663 6163 2566231 2565623 609 pir: A70866Mycobacterium tuberculosis 56.8 80.9 199 hypothetical protein H37RvRv2466c 2664 6164 2566345 2568945 2601 sp: AMPN_STRLI Streptomyceslividans pepN 47.5 70.5 890 aminopeptidase N 2665 6165 2569211 25702931083 pir: B70206 Borrelia burgdorferi BB0852 25.1 58.1 358 hypotheticalprotein 2666 6166 2571460 2570309 1152 2667 6167 2571510 2572175 6662668 6168 2572193 2572348 156 2669 6169 2572677 2572351 327 gp:AF139916_3 Brevibacterium linens ATCC 61.5 81.7 104 phytoene desaturase9175 crtI 2670 6170 2572977 2572807 171 2671 6171 2573770 2573393 3782672 6172 2573864 2572659 1206 sp: CRTJ_MYXXA Myxococcus xanthus DK105031.2 63.8 381 phytoene dehydrogenase carA2 2673 6173 2574718 2573843 876sp: CRTB_STRGR Streptomyces griseus JA3933 31.4 58.6 290 phytoenesynthase crtB 2674 6174 2575898 2574780 1119 gp: LMAJ9627_3 Listeriamonocytogenes lltB 25.8 47.7 392 multidrug resistance transporter 26756175 2577213 2575981 1233 2676 6176 2578872 2577232 1641 gp: SYOATPBP_2Synechococcus elongatus 41.3 71.6 538 ABC transporter ATP-bindingprotein 2677 6177 2579760 2578879 882 sp: DPPC_BACFI Bacillus firmus OF4dppC 38.8 73.8 286 dipeptide transport system permease protein 2678 61782580707 2579769 939 pir: S47696 Escherichia coli K12 nikB 33.2 62.0 316nickel transport system permease protein 2679 6179 2582417 2580711 17072680 6180 2582564 2584504 1941 2681 6181 2584613 2585926 1314 sp:ARGD_CORGL Corynebacterium glutamicum 31.4 63.5 411 acetylornithineaminotransferase ATCC 13032 argD 2682 6182 2586180 2587763 1584 pir:A70539 Mycobacterium tuberculosis 25.1 47.9 482 hypothetical proteinH37Rv Rv1128c 2683 6183 2587976 2588722 747 sp: YA26_MYCTU Mycobacteriumtuberculosis 49.1 79.4 218 hypothetical membrane protein H37Rv Rv03642684 6184 2589432 2588725 708 sp: PHBB_CHRVI Chromatium vinosum D phbB28.1 60.0 235 acetoacetyl CoA reductase 2685 6185 2589565 2590302 738pir: A40046 Streptomyces coelicolor actII 26.7 55.0 240 transcriptionalregulator, TetR family 2686 6186 2590697 2591137 441 GSP: Y74375Neisseria meningitidis 38.0 47.0 94 polypeptides predicted to be usefulantigens for vaccines and diagnostics 2687 6187 2592365 2591574 792 gp:AF106002_1 Pseudomonas putida GM73 31.1 65.1 238 ABC transporterATP-binding protein ttg2A 2688 6188 2592402 2592794 393 gp: MLCB1610_9Mycobacterium leprae 53.2 77.0 126 globin MLCB1610.14c 2689 6189 25928382593965 1128 sp: CHRA_PSEAE Pseudomonas aeruginosa 27.3 60.4 396chromate transport protein Plasmid pUM505 chrA 2690 6190 2594594 2593968627 pir: A70867 Mycobacterium tuberculosis 37.8 68.9 196 hypotheticalprotein H37Rv Rv2474c 2691 6191 2595061 2594597 465 gp: SC6D10_19Streptomyces coelicolor A3(2) 36.2 61.4 127 hypothetical proteinSC6D10.19c 2692 6192 2595808 2595188 621 2693 6193 2595983 2595822 162pir: B72589 Aeropyrum pernix K1 APE1182 36.4 60.0 55 hypotheticalprotein 2694 6194 2597715 2596048 1668 sp: YJJK_ECOLI Escherichia coliK12 yjjK 52.8 79.6 563 ABC transporter ATP-binding protein 2695 61952598483 2597869 615 pir: E70867 Mycobacterium tuberculosis 31.4 62.2 172hypothetical protein H37Rv Rv2478c 2696 6196 2600764 2598662 2103 sp:Y05L_MYCLE Mycobacterium leprae o659 28.0 56.7 700 hypothetical membraneprotein 2697 6197 2601461 2602879 1419 pir: C69676 Bacillus subtilisphoB 28.0 52.6 536 alkaline phosphatase 2698 6198 2604573 2605502 9302699 6199 2604583 2603945 639 2700 6200 2605520 2604609 912 sp:MSMG_STRMU Streptococcus mutans 39.1 76.3 279 multiple sugar-bindingtransport INGBRITT msmG system permease protein 2701 6201 26063692605527 843 sp: MSMF_STRMU Streptococcus mutans 27.4 67.5 292 multiplesugar-binding transport INGBRITT msmF system permease protein 2702 62022606444 2608117 1674 2703 6203 2607889 2606561 1329 prf: 2206392CThermoanaerobacterium 28.8 63.2 462 maltose-binding protein thermosulamyE 2704 6204 2609426 2608185 1242 2705 6205 2610639 2609512 1128 prf:2308356A Streptomyces reticuli msiK 59.1 79.8 386 ABC transporterATP-binding protein (ABC-type sugar transport protein) orcellobiose/maltose transport protein 2706 6206 2611523 2612272 750 27076207 2611531 2610848 684 prf: 2317468A Schizosaccharomyces pombe 37.772.7 154 dolichol phosphate mannose dpm1 synthase 2708 6208 26124622613151 690 2709 6209 2613712 2614500 789 prf: 2516398E Rhodococcusrhodochrous 67.2 89.4 207 aldehyde dehydrogenase plasmid pRTL1 orf5 27106210 2614649 2615410 762 prf: 2513418A Synechococcus sp. PCC7942 48.673.8 183 circadian phase modifier cpmA 2711 6211 2615451 2615795 3452712 6212 2617120 2615939 1182 pir: A72312 Thermotoga maritima MSB8 35.064.6 412 hypothetical membrane protein TM0964 2713 6213 2617246 2617995750 sp: GIP_ECOLI Escherichia coli K12 gip 41.2 69.4 255glyoxylate-induced protein 2714 6214 2618072 2618869 798 pir: E70761Mycobacterium tuberculosis 40.0 57.0 258 ketoacyl reductase H37Rv Rv15442715 6215 2618882 2619538 657 sp: ORN_ECOLI Escherichia coli K12 orn48.0 78.8 179 oligoribonuclease 2716 6216 2620728 2619541 1188 prf:2409378A Salmonella enterica iroD 26.0 50.9 454 ferric enterochelinesterase 2717 6217 2622181 2620973 1209 pir: C70870 Mycobacteriumtuberculosis 48.5 71.9 398 lipoprotein H37Rv Rv2518c lppS 2718 62182622961 2623605 645 2719 6219 2623770 2623621 150 2720 6220 26238032624048 246 2721 6221 2625358 2624051 1308 gp: SCU53587_1Corynebacterium glutamicum 99.5 99.8 436 transposase (IS1207) ATCC 210862722 6222 2625600 2625806 207 2723 6223 2626447 2625809 639 2724 62242627924 2628376 453 gp: AF085239_1 Salmonella typhimurium KP1001 32.863.4 131 transcriptional regulator cytR 2725 6225 2628121 2626493 1629sp: GLSK_RAT Rattus norvegicus SPRAGUE- 35.2 69.3 358 glutaminase DAWLEYKIDNEY 2726 6226 2628376 2628852 477 pir: A36940 Bacillus subtilis 168degA 42.3 72.2 97 sporulation-specific degradation regulator protein2727 6227 2628878 2628324 555 2728 6228 2628926 2630479 1554 sp:UXAC_ECOLI Escherichia coli K12 uxaC 29.0 60.9 335 uronate isomerase2729 6229 2630636 2631136 501 2730 6230 2631270 2632466 1197 prf:1814452C Zea diploperennis perennial 32.0 45.0 291 hypothetical proteinteosinte 2731 6231 2632543 2633100 558 prf: 2324444A Mycobacterium aviumpncA 48.1 74.6 185 pyrazinamidase/nicotinamidase 2732 6232 26334182633146 273 pir: E70870 Mycobacterium tuberculosis 42.7 80.0 75hypothetical protein H37Rv Rv2520c 2733 6233 2633600 2634064 465 sp:BCP_ECOLI Escherichia coli K12 bcp 46.8 73.8 141 bacterioferritincomigratory protein 2734 6234 2634116 2634751 636 gp: SCI11_1Streptomyces coelicolor A3(2) 32.5 61.4 114 bacterial regulatoryprotein, tetR SCI11.01c family 2735 6235 2635151 2634747 405 gp:BAY15081_1 Corynebacterium 56.6 75.9 145 phosphopantethiene proteinammoniagenes ATCC 6871 ppt1 transferase 2736 6236 2636589 2635165 1425gp: AF237667_1 Corynebacterium glutamicum 52.4 85.6 473 lincomycinresistance protein lmrB 2737 6237 2636845 2637168 324 pir: S76537Synechocystis sp. PCC6803 30.1 54.0 113 hypothetical membrane protein2738 6238 2637653 2637240 414 2739 6239 2647627 2638649 8979 pir: S2047Corynebacterium 62.3 83.6 3029 fatty-acid synthase ammoniagenes fas 27406240 2649416 2648235 1182 gp: SC4A7_14 Streptomyces coelicolor A3(2)25.3 55.2 404 hypothetical protein SC4A7.14 2741 6241 2649550 2650164615 pir: D70716 Mycobacterium tuberculosis 40.4 60.9 230 peptidase H37RvRv0950c 2742 6242 2650441 2650902 462 sp: Y077_MYCT Mycobacteriumtuberculosis 40.2 67.9 112 hypothetical membrane protein H37Rv Rv1343c2743 6243 2650986 2651339 354 sp: Y076_MYCLE Mycobacterium leprae 37.269.0 113 hypothetical membrane protein B1549_F2_59 2744 6244 26520372651420 618 sp: Y03Q_MYCTU Mycobacterium tuberculosis 55.0 76.7 202hypothetical protein H37Rv Rv1341 2745 6245 2652801 2652067 735 sp:RNPH_PSEAE Pseudomonas aeruginosa 60.2 81.4 236 ribonuclease PH ATCC15692 rph 2746 6246 2653254 2653009 246 2747 6247 2654018 2653326 6932748 6248 2654660 2654079 582 2749 6249 2656236 2654875 1362 sp:Y029_MYCTU Mycobacterium tuberculosis 29.0 58.2 428 hypotheticalmembrane protein H37Rv SC8A6.09c 2750 6250 2656452 2656985 534 gp:AF121000_8 Corynebacterium glutamicum 92.1 97.2 175 transposase (IS1628)22243 R-plasmid pAG1 tnpB 2751 6251 2657633 2656974 660 2752 62522658500 2657736 765 sp: Y03O_MYCLE Mycobacterium leprae ats 46.0 74.4250 arylsulfatase 2753 6253 2659457 2658606 852 prf: 2516259ACorynebacterium glutamicum 99.3 99.3 284 D-glutamate racemase ATCC 13869murI 2754 6254 2659496 2660131 636 2755 6255 2660638 2660147 492 gp:SCE22_22 Streptomyces coelicolor A3(2) 44.2 70.8 147 bacterialregulatory protein, marR SCE22.22 family 2756 6256 2661417 2660671 747sp: Y03M_MYCTU Mycobacterium tuberculosis 38.2 69.3 225 hypotheticalmembrane protein H37Rv Rv1337 2757 6257 2661565 2662455 891 2758 62582662376 2661417 960 pir: A47039 Flavobacterium sp. nylC 30.2 58.3 321endo-type 6-aminohexanoate oligomer hydrolase 2759 6259 2662867 2662331537 sp: Y03H_MYCTU Mycobacterium tuberculosis 35.0 58.5 200 hypotheticalprotein H37Rv Rv1332 2760 6260 2663182 2662883 300 sp: Y03G_MYCTUMycobacterium tuberculosis 57.1 77.1 105 hypothetical protein H37RvRv1331 2761 6261 2663437 2664060 624 2762 6262 2664060 2665397 1338 sp:Y03F_MYCTU Mycobacterium tuberculosis 61.2 80.8 428 hypothetical proteinH37Rv Rv1330c 2763 6263 2665687 2665992 306 2764 6264 2666115 26678541740 prf: 1816252A Escherichia coli dinG 25.2 53.3 647 ATP-dependenthelicase 2765 6265 2668760 2667870 891 sp: Y0A8_MYCTU Mycobacteriumtuberculosis 29.7 60.1 313 hypothetical membrane protein H37Rv Rv25602766 6266 2669561 2668839 723 pir: T34684 Streptomyces coelicolor A3(2)39.0 52.0 222 hypothetical protein SC1B5.06c 2767 6267 2670573 26695571017 sp: SERB_ECOLI Escherichia coli K12 serB 38.7 61.0 310phosphoserine phosphatase 2768 6268 2671126 2672721 1596 2769 62692672805 2671063 1743 pir: D45335 Mycobacterium tuberculosis 46.8 74.4575 cytochrome c oxidase chain I H37Rv Rv3043c 2770 6270 2672950 2673255306 2771 6271 2674339 2673338 1002 gp: AF112536_1 Corynebacteriumglutamicum 99.7 99.7 334 ribonucleotide reductase beta-chain ATCC 13032nrdF 2772 6272 2674804 2675289 486 sp: FTNA_ECOLI Escherichia coli K12ftnA 31.5 64.2 159 ferritin 2773 6273 2675491 2676240 750 gp:SCA32WHIH_4 Streptomyces coelicolor A3(2) 32.8 60.2 256 sporulationtranscription factor whiH 2774 6274 2676902 2676243 660 pir: I40339Corynebacterium glutamicum 27.6 60.4 225 iron dependent repressor orATCC 13869 dtxR diptheria toxin repressor 2775 6275 2676940 2677377 438sp: TIR2_YEAST Saccharomyces cerevisiae 24.2 62.1 124 cold shock proteinTIR2 precursor YPH148 YOR010C TIR2 2776 6276 2677193 2676918 276 pir:C69281 Archaeoglobus fulgidus AF0251 50.0 86.0 50 hypothetical membraneprotein 2777 6277 2679598 2677478 2121 gp: AF112535_3 Corynebacteriumglutamicum 99.9 100.0 707 ribonucleotide reductase alpha- ATCC 13032nrdE chain 2778 6278 2680470 2680784 315 2779 6279 2681363 2681223 141SP: RL36_RICPR Rickettsia prowazekii 58.0 79.0 41 50S ribosomal proteinL36 2780 6280 2681546 2682376 831 sp: NADE_BACSU Bacillus subtilis 168nadE 55.6 78.1 279 NH3-dependent NAD(+) synthetase 2781 6281 26815562681464 93 2782 6282 2683119 2683616 498 2783 6283 2683125 2682379 747pir: S76790 Synechocystis sp. PCC6803 30.7 56.4 257 hypothetical proteinstr1563 2784 6284 2683418 2683131 288 pir: G70922 Mycobacteriumtuberculosis 41.7 68.8 96 hypothetical protein H37Rv Rv3129 2785 62852684646 2683627 1020 sp: ADH2_BACST Bacillus stearothermophilus 26.152.8 337 alcohol dehydrogenase DSM 2334 adh 2786 6286 2684919 26862891371 sp: MMGE_BACSU Bacillus subtilis 168 mmgE 27.0 56.0 459 Bacillussubtilis mmg (for mother cell metabolic genes) 2787 6287 2686315 2687148834 pir: T05174 Arabidopsis thaliana T6K22.50 33.8 66.2 284 hypotheticalprotein 2788 6288 2688240 2687449 792 2789 6289 2690050 2688389 1662 sp:PGMU_ECOLI Escherichia coli K12 pgm 61.7 80.6 556 phosphoglucomutase2790 6290 2690150 2690437 288 pir: F70650 Mycobacterium tuberculosis41.7 64.3 84 hypothetical membrane protein H37Rv Rv3069 2791 62912690437 2690760 324 pir: D71843 Helicobacter pylori J99 jhp1146 25.461.5 122 hypothetical membrane protein 2792 6292 2690773 2691564 792 sp:YCSI_BACSU Bacillus subtilis 168 ycsI 51.2 79.1 254 hypothetical protein2793 6293 2691689 2693053 1365 gp: AF126281_1 Rhodococcus erythropolis24.2 48.6 496 transposase (IS1676) 2794 6294 2693299 2694918 1620 sp:CSP1_CORGL Corynebacterium glutamicum 24.8 49.6 355 major secretedprotein PS1 protein (Brevibacterium flavum) ATCC precursor 17965 csp12795 6295 2694926 2695279 354 2796 6296 2695554 2695718 165 2797 62972695766 2695320 447 2798 6298 2695812 2697212 1401 gp: AF126281_1Rhodococcus erythropolis 24.6 46.6 500 transposase (IS1676) 2799 62992698150 2697383 768 2800 6300 2699531 2698194 1338 sp: GLTT_BACCABacillus subtilis 168 30.8 66.2 438 proton/sodium-glutamate symportprotein 2801 6301 2700920 2701612 693 2802 6302 2702466 2699926 2541 gp:SCE25_30 Streptomyces coelicolor A3(2) 33.0 69.0 873 ABC transporterSCE25.30 2803 6303 2702466 2703356 891 2804 6304 2703194 2702487 708 gp:SAU18641_2 Staphylococcus aureus 45.4 79.8 218 ABC transporterATP-binding protein 2805 6305 2704314 2704586 273 PIR: F81516Chlamydophila pneumoniae 60.0 67.0 84 hypothetical protein AR39 CP09872806 6306 2704835 2704975 141 PIR: F81737 Chlamydia muridarum Nigg 71.075.0 42 hypothetical protein TC0129 2807 6307 2709878 2710555 678 28086308 2710637 2711308 672 prf: 2509388L Streptomyces collinus Tu 189228.1 54.1 196 oxidoreductase or dehydrogenase ansG 2809 6309 27118502712374 525 sp: Y089_MYCTU Mycobacterium tuberculosis 25.9 51.2 205methyltransferase H37Rv Rv0089 2810 6310 2713181 2713453 273 GSP: Y35814Chlamydia pneumoniae 61.0 66.0 84 hypothetical protein 2811 6311 27137022713842 141 PIR: F81737 Chlamydia muridarum Nigg 71.0 75.0 42hypothetical protein TC0129 2812 6312 2718187 2717993 195 2813 63132719689 2718436 1254 sp: MURA_ACICA Acinetobacter calcoaceticus 44.875.3 417 UDP-N-acetylglucosamine 1- NCIB 8250 murAcarboxyvinyltransferase 2814 6314 2719750 2720319 570 sp: Y02Y_MYCTUMycobacterium tuberculosis 66.3 84.2 190 hypothetical protein H37RvRv1314c 2815 6315 2721227 2720385 843 gp: SC2G5_15 Streptomycescoelicolor A3(2) 45.9 69.0 281 transcriptional regulator SC2G5.15c 28166316 2721702 2721295 408 2817 6317 2721934 2722857 924 sp: CYSK_BACSUBacillus subtilis 168 cysK 57.1 84.6 305 cysteine synthase 2818 63182723064 2723609 546 prf: 2417357C Azotobacter vinelandii cysE2 61.1 79.7172 O-acetylserine synthase 2819 6319 2724057 2723770 288 gp:AE002024_10 Deinococcus radiodurans R1 36.1 65.1 83 hypothetical proteinDR1844 2820 6320 2725359 2724478 882 sp: SUCD_COXBU Coxiella burnetiiNine Mile Ph I 52.9 79.4 291 succinyl-CoA synthetase alpha sucD chain2821 6321 2725619 2725843 225 PIR: F72706 Aeropyrum pernix K1 APE106942.0 43.0 75 hypothetical protein 2822 6322 2726577 2725384 1194 sp:SUCC_BACSU Bacillus subtilis 168 sucC 39.8 73.0 400 succinyl-CoAsynthetase beta chain 2823 6323 2727145 2726786 360 2824 6324 27281332727399 735 gp: AF058302_5 Streptomyces roseofulvus frnE 38.5 71.8 213frenolicin gene E product 2825 6325 2729025 2728207 819 2826 63262730916 2729378 1539 sp: CAT1_CLOKL Clostridium kluyveri cat1 cat1 47.977.8 501 succinyl-CoA coenzyme A transferase 2827 6327 2731376 27325181143 sp: NIR3_AZOBR Azospirillum brasilense ATCC 38.6 68.5 321transcriptional regulator 29145 ntrC 2828 6328 2732230 2731424 807 28296329 2732636 2733367 732 pir: E70810 Mycobacterium tuberculosis 46.581.7 213 phosphate transport system H37Rv Rv0821c phoY-2 regulatoryprotein 2830 6330 2734351 2733455 897 pir: S68595 Pseudomonas aeruginosapstB 58.8 82.8 255 phosphate-specific transport component 2831 63312735184 2734264 921 gp: MTPSTA1_1 Mycobacterium tuberculosis 51.4 82.2292 phosphate ABC transport system H37Rv Rv0830 pstA1 permease protein2832 6332 2736215 2735202 1014 pir: A70584 Mycobacterium tuberculosis50.2 78.5 325 phosphate ABC transport system H37Rv Rv0829 pstC2 permeaseprotein 2833 6333 2737538 2736414 1125 pir: H70583 Mycobacteriumtuberculosis 40.0 56.0 369 phosphate-binding protein S-3 H37Rv phoS2precursor 2834 6334 2738711 2737836 876 gp: SCD84_18 Streptomycescoelicolor A3(2) 34.3 60.0 315 acetyltransferase SCD84.18c 2835 63352738771 2739553 783 2836 6336 2740650 2739556 1095 sp: BMRU_BACSUBacillus subtilis 168 bmrU 24.7 55.2 344 hypothetical protein 2837 63372740670 2741356 687 pir: E70809 Mycobacterium tuberculosis 44.9 74.2 225hypothetical protein H37Rv Rv0813c 2838 6338 2742577 2741636 942 gp:AF193846_1 Solanum tuberosum BCAT2 28.6 56.0 259 branched-chain aminoacid aminotransferase 2839 6339 2742685 2743785 1101 gp: AB003158_6Corynebacterium 58.5 79.0 352 hypothetical protein ammoniagenes ATCC6872 ORF4 2840 6340 2744010 2744222 213 pir: B70809 Mycobacteriumtuberculosis 58.6 81.0 58 hypothetical protein H37Rv Rv0810c 2841 63412745954 2744881 1074 gp: AB003158_5 Corynebacterium 81.0 94.2 3475′-phosphoribosyl-5-aminoimidazole ammoniagenes ATCC 6872 synthetasepurM 2842 6342 2747564 2746083 1482 gp: AB003158_4 Corynebacterium 70.389.0 482 amidophosphoribosyl transferase ammoniagenes ATCC 6872 purF2843 6343 2748057 2747683 375 pir: H70536 Mycobacterium tuberculosis57.3 75.8 124 hypothetical protein H37Rv Rv0807 2844 6344 27480952749111 1017 gp: AB003158_2 Corynebacterium 75.9 94.0 315 hypotheticalprotein ammoniagenes ATCC 6872 ORF2 2845 6345 2749902 2749162 741 gp:AB003158_1 Corynebacterium 67.7 87.1 217 hypothetical membrane proteinammoniagenes ATCC 6872 ORF1 2846 6346 2751918 2752103 186 GP:SSU18930_214 Sulfolobus solfataricus 64.0 71.0 42 hypothetical protein2847 6347 2752312 2750027 2286 gp: AB003162_3 Corynebacterium 77.6 89.5763 5′-phosphoribosyl-N- ammoniagenes ATCC 6872 formylglycinamidinesynthetase purL 2848 6348 2752402 2753121 720 2849 6349 2752995 2752327669 gp: AB003162_2 Corynebacterium 80.3 93.3 223 5′-phosphoribosyl-N-ammoniagenes ATCC 6872 formylglycinamidine synthetase purQ 2850 63502753237 2752995 243 gp: AB003162_1 Corynebacterium 81.0 93.7 79hypothetical protein ammoniagenes ATCC 6872 purorf 2851 6351 27532982753819 522 2852 6352 2753804 2753328 477 prf: 2420329A Lactococcuslactis gpo 46.2 77.9 158 gluthatione peroxidase 2853 6353 27539922756739 2748 prf: 2216389A Aeromonas hydrophila JMP636 28.0 51.5 965extracellular nuclease nucH 2854 6354 2756851 2757126 276 2855 63552757815 2757129 687 pir: C70709 Mycobacterium tuberculosis 37.4 68.7 211hypothetical protein H37Rv Rv0784 2856 6356 2759200 2757863 1338 sp:DCTA_SALTY Salmonella typhimurium LT2 49.0 81.6 414 C4-dicarboxylatetransporter dctA 2857 6357 2761649 2759532 2118 prf: 2408266APseudomonas sp. WO24 dapb1 41.8 70.6 697 dipeptidyl aminopeptidase 28586358 2762452 2761829 624 2859 6359 2762675 2761785 891 gp: AB003161_3Corynebacterium 70.1 89.1 294 5′-phosphoribosyl-4-N- ammoniagenes ATCC6872 succinocarboxamide-5-amino purC imidazole synthetase 2860 63602764931 2763504 1428 gp: AB003161_2 Corynebacterium 85.3 95.0 477adenylosuccino lyase ammoniagenes ATCC 6872 purB 2861 6361 27661352764978 1158 sp: AAT_SULSO Sulfolobus solfataricus ATCC 28.1 62.3 395aspartate aminotransferase 49255 2862 6362 2767420 2766158 1263 gp:AB003161_1 Corynebacterium 71.1 86.4 425 5′-phosphoribosylglycinamideammoniagenes ATCC 6872 synthetase purD 2863 6363 2767580 2767993 414 sp:YHIT_MYCLE Mycobacterium leprae u296a 53.7 80.2 136 histidine triad(HIT) family protein 2864 6364 2768137 2767703 435 2865 6365 27690952768343 753 pir: S62195 Methanosarcina barkeri orf3 26.8 56.4 243hypothetical protein 2866 6366 2770511 2769156 1356 sp: DTPT_LACLALactococcus lactis subsp. lactis 30.1 67.6 469 di-/tripeptide transpoterdipT 2867 6367 2770714 2771982 1269 sp: BIOA_CORGL Corynebacteriumglutamicum 95.7 98.8 423 adenosylmethionine-8-amino-7- (Brevibacteriumflavum) MJ233 oxononanoate aminotransferase or bioA7,8-diaminopelargonic acid aminotransferase 2868 6368 2771989 2772660672 sp: BIOD_CORGL Corynebacterium glutamicum 98.7 99.6 224 dethiobiotinsynthetase (Brevibacterium flavum) MJ233 bioD 2869 6369 2774098 27726441455 gp: AF049873_3 Lactococcus lactis M71plasmid 31.3 70.5 335two-component system sensor pND306 histidine kinase 2870 6370 27748142774110 705 prf: 2222216A Thermotoga maritima drrA 42.0 72.7 231two-component system regulatory protein 2871 6371 2775689 2774937 753sp: TIPA_STRLI Streptomyces lividans tipA 37.4 69.5 249 transcriptionalactivator 2872 6372 2776879 2775740 1140 prf: 2419350A Arthrobacter sp.DK-38 30.9 53.9 382 metal-activated pyridoxal enzyme or low specificityD-Thr aldolase 2873 6373 2778504 2776768 1737 gp: ECOPOXB8G_1Escherichia coli K12 poxB 46.3 75.8 574 pyruvate oxidase 2874 63742778965 2780446 1482 prf: 2212334B Staphylococcus aureus plasmid 33.368.9 504 multidrug efflux protein pSK23 qacB 2875 6375 2780439 2780969531 sp: YCDC_ECOLI Escherichia coli K12 ycdC 30.4 68.5 92transcriptional regulator 2876 6376 2780996 2782315 1320 pir: D70551Mycobacterium tuberculosis 45.6 78.4 421 hypothetical membrane proteinH37Rv Rv2508c 2877 6377 2784481 2782340 2142 2878 6378 2785615 2784656960 gp: AF096929_2 Rhodococcus erythropolis SQ1 34.3 62.1 3033-ketosteroid dehydrogenase kstD1 2879 6379 2786355 2785651 705 sp:ALSR_BACSU Bacillus subtilis 168 alsR 37.1 69.0 232 transcriptionalregulator, LysR family 2880 6380 2787782 2788594 813 pir: C70982Mycobacterium tuberculosis 28.4 52.9 278 hypothetical protein H37RvRv3298c lpqC 2881 6381 2789399 2788587 813 pir: C69862 Bacillus subtilis168 ykrA 26.7 55.6 288 hypothetical protein 2882 6382 2789935 2789477459 2883 6383 2790152 2790550 399 pir: A45264 Oryctolagus cuniculuskidney 28.6 50.7 140 hypothetical protein cortex rBAT 2884 6384 27909462792448 1503 pir: B70798 Mycobacterium tuberculosis 36.0 64.0 464hypothetical membrane protein H37Rv Rv3737 2885 6385 2792531 2792857 327pir: S41307 Streptomyces griseus hrdB 32.3 50.3 155 transcriptioninitiation factor sigma 2886 6386 2792873 2794327 1455 sp: TPS1_SCHPOSchizosaccharomyces pombe 38.8 66.7 487 trehalose-6-phosphate synthasetps1 2887 6387 2794300 2794812 513 2888 6388 2794870 2795637 768 sp:OTSB_ECOLI Escherichia coli K12 otsB 27.4 57.6 245 trehalose-phosphatase2889 6389 2796749 2795676 1074 sp: CCPA_BACME Bacillus megaterium ccpA24.7 60.2 344 glucose-resistance amylase regulator 2890 6390 27968652797806 942 sp: ZNUA_HAEIN Haemophilus influenzae Rd 22.4 46.7 353high-affinity zinc uptake system HI0119 znuA protein 2891 6391 27978202798509 690 gp: AF121672_2 Staphylococcus aureus 8325-4 31.4 63.2 223ABC transporter mreA 2892 6392 2798837 2799391 555 pir: E70507Mycobacterium tuberculosis 60.0 87.4 135 hypothetical membrane proteinH37Rv Rv2060 2893 6393 2799535 2801034 1500 pir: A69426 Archaeoglobusfulgidus 23.4 52.5 303 transposase (ISA0963-5) 2894 6394 2801113 2801313201 2895 6395 2803246 2801558 1689 gp: AF096929_2 Rhodococcuserythropolis SQ1 32.1 62.0 561 3-ketosteroid dehydrogenase kstD1 28966396 2803996 2803250 747 2897 6397 2804691 2804074 618 pir: B72359Thermotoga maritima MSB8 34.3 56.4 204 lipopolysaccharide biosynthesisbplA protein or oxidoreductase or dehydrogenase 2898 6398 28051102804676 435 sp: MI2D_BACSU Bacillus subtilis 168 idh or iolG 35.2 69.5128 dehydrogenase or myo-inositol 2- dehydrogenase 2899 6399 28059672805113 855 sp: SHIA_ECOLI Escherichia coli K12 shiA 30.5 67.5 292shikimate transport protein 2900 6400 2806441 2806016 426 sp: SHIA_ECOLIEscherichia coli K12 shiA 43.1 80.8 130 shikimate transport protein 29016401 2807252 2806599 654 gp: SC5A7_19 Streptomyces coelicolor A3(2) 32.655.7 212 transcriptional regulator SC5A7.19c 2902 6402 2808364 2807426939 sp: PT56_YEAST Saccharomyces cerevisiae 22.8 47.3 334 ribosomal RNAribose methylase or YOR201C PET56 tRNA/rRNA methyltransferase 2903 64032809778 2808399 1380 sp: SYC_ECOLI Escherichia coli K12 cysS 42.2 68.8464 cysteinyl-tRNA synthetase 2904 6404 2811806 2809824 1983 prf:2511335C Lactococcus lactis sacB 47.0 77.0 668 PTS system, enzyme IIsucrose protein (sucrose-specific IIABC component) 2905 6405 28132582811960 1299 gp: AF205034_4 Clostridium acetobutylicum 35.3 56.9 473sucrose 6-phosphate hydrolase or ATCC 824 scrB sucrase 2906 6406 28140372813279 759 sp: NAGB_ECOLI Escherichia coli K12 nagB 38.3 69.4 248glucosamine-6-phosphate isomerase 2907 6407 2815232 2814081 1152 sp:NAGA_VIBFU Vibrio furnissii SR1514 manD 30.2 60.3 368N-acetylglucosamine-6-phosphate deacetylase 2908 6408 2815458 2816393936 sp: DAPA_ECOLI Escherichia coli K12 dapA 28.2 62.1 298dihydrodipicolinate synthase 2909 6409 2816409 2817317 909 sp: GLK_STRCOStreptomyces coelicolor A3(2) 28.7 57.6 321 glucokinase SC6E10.20c glk2910 6410 2817363 2818058 696 prf: 2516292A Clostridium perfringens NCTC36.4 68.6 220 N-acetylmannosamine-6-phosphate 8798 nanE epimerase 29116411 2818313 2818137 177 2912 6412 2819564 2818350 1215 sp: NANH_MICVIMicromonospora viridifaciens 24.8 50.3 439 sialidase precursor ATCC31146 nadA 2913 6413 2820285 2819557 729 gp: AF181498_1 Rhizobium etliansR 26.6 57.2 222 L-asparagine permease operon repressor 2914 64142820584 2822191 1608 gp: BFU64514_1 Bacillus firmus OF4 dppA 22.5 51.4560 dipeptide transporter protein or heme-binding protein 2915 64152822387 2823337 951 sp: DPPB_BACFI Bacillus firmus OF4 dappB 31.9 64.3342 dipeptide transport system permease protein 2916 6416 28242742825341 1068 sp: OPPD_BACSU Bacillus subtilis 168 oppD 46.5 78.3 314oligopeptide transport ATP-binding protein 2917 6417 2825341 2826156 816sp: OPPF_LACLA Lactococcus lactis oppF 43.4 78.7 258 oligopeptidetransport ATP-binding protein 2918 6418 2826835 2826215 621 sp:RHTB_ECOLI Escherichia coli K12 rhtB 28.5 62.7 193 homoserine/homoserinlactone efflux protein or lysE type translocator 2919 6419 28269222827404 483 prf: 2309303A Bradyrhizobium japonicum lrp 31.0 66.2 142leucine-responsive regulatory protein 2920 6420 2827817 2827458 360 29216421 2828383 2827904 480 pir: C70607 Mycobacterium tuberculosis 55.986.2 152 hypothetical protein H37Rv Rv3581c 2922 6422 2829146 2828379768 sp: Y18T_MYCTU Mycobacterium tuberculosis 46.4 71.5 235 hypotheticalprotein H37Rv Rv3582c 2923 6423 2829749 2829156 594 pir: H70803Mycobacterium tuberculosis 73.3 91.1 157 transcription factor H37RvRv3583c 2924 6424 2830057 2830779 723 prf: 2214304A Mycobacteriumtuberculosis 43.5 70.0 223 two-component system response H37Rv Rv3246cmtrA regulator 2925 6425 2830779 2831894 1116 sp: BAES_ECOLI Escherichiacoli K12 baeS 29.3 67.7 341 two-component system sensor histidine kinase2926 6426 2832085 2832666 582 2927 6427 2832790 2834181 1392 sp:RADA_ECOLI Escherichia coli K12 radA 41.5 74.3 463 DNA repair proteinRadA 2928 6428 2834188 2835285 1098 sp: YACK_BACSU Bacillus subtilis 168yacK 40.3 73.3 345 hypothetical protein 2929 6429 2835969 2835283 687pir: D70804 Mycobacterium tuberculosis 29.4 53.3 231 hypotheticalprotein H37Rv Rv3587c 2930 6430 2837499 2836048 1452 gp: PPU96338_1Pseudomonas putida NCIMB 59.5 85.1 471 p-hydroxybenzaldehyde 9866plasmid pRA4000 dehydrogenase 2931 6431 2837737 2837591 147 2932 64322838576 2837956 621 pir: T08204 Chlamydomonas reinhardtii ca1 36.7 66.2210 mitochondrial carbonate dehydratase beta 2933 6433 2838643 2839521879 gp: AF121797_1 Streptomyces antibioticus IMRU 48.4 70.7 283A/G-specific adenine glycosylase 3720 mutY 2934 6434 2839562 28407161155 2935 6435 2841063 2840758 306 2936 6436 2841075 2841848 774 gp:AB009078_1 Brevibacterium saccharolyticum 99.2 99.6 258 L-2.3-butanedioldehydrogenase 2937 6437 2842130 2842453 324 2938 6438 2842493 2843233741 2939 6439 2843405 2843716 312 2940 6440 2843722 2843432 291 pir:E70552 Mycobacterium tuberculosis 48.5 69.1 97 hypothetical proteinH37Rv Rv3592 2941 6441 2845139 2845558 420 GSP: Y29188 Pseudomonasaeruginosa 57.0 63.0 99 virulence factor ORF24222 2942 6442 28458892846101 213 GSP: Y29193 Pseudomonas aeruginosa 54.0 55.0 72 virulencefactor ORF25110 2943 6443 2846186 2846506 321 GSP: Y29193 Pseudomonasaeruginosa 74.0 75.0 55 virulence factor ORF25110 2944 6444 28469402844166 2775 sp: MECB_BACSU Bacillus subtilis 168 mecB 58.5 86.2 832ClpC adenosine triphosphatase/ ATP-binding proteinase 2945 6445 28472292848659 1431 gp: AB035643_1 Bacillus cereus ts-4 impdh 37.1 70.2 469inosine monophosphate dehydrogenase 2946 6446 2848769 2849779 1011 pir:JC6117 Rhodococcus rhodochrous nitR 24.7 62.7 316 transcription factor2947 6447 2850031 2851815 1785 sp: PH2M_TRICU Trichosporon cutaneum ATCC33.5 60.9 680 phenol 2-monooxygenase 46490 2948 6448 2852017 28537321716 2949 6449 2853769 2855709 1941 2950 6450 2855795 2857516 1722 29516451 2859044 2859205 162 2952 6452 2859055 2857613 1443 gp: AF237667_1Corynebacterium glutamicum 100.0 100.0 481 lincomycin resistance proteinlmrB 2953 6453 2860145 2859195 951 pir: G70807 Mycobacteriumtuberculosis 26.7 55.8 240 hypothetical protein H37Rv Rv3517 2954 64542862082 2860505 1578 gp: AB012100_1 Bacillus stearothermophilus lysS41.7 71.2 511 lysyl-tRNA synthetase 2955 6455 2862929 2862132 798 gp:CGPAN_2 Corynebacterium glutamicum 29.9 52.6 268 pantoate—beta-alanineligase ATCC 13032 panC 2956 6456 2863621 2862929 693 2957 6457 28644212863624 798 2958 6458 2864848 2864384 465 gp: MLCB2548_4 Mycobacteriumleprae 29.0 69.6 138 hypothetical membrane protein MLCB2548.04c 29596459 2865343 2864867 477 sp: HPPK_METEX Methylobacterium extorquens 42.469.0 158 2-amino-4-hydroxy-6- AM1 folK hydroxymethyldihydropteridinepyrophosphokinase 2960 6460 2865735 2865346 390 sp: FOLB_BACSU Bacillussubtilis 168 folB 38.1 69.5 118 dihydroneopterin aldolase 2961 64612866567 2865731 837 gp: AB028656_1 Mycobacterium leprae folP 51.5 75.0268 dihydropteroate synthase 2962 6462 2867173 2866586 588 sp:GCH1_BACSU Bacillus subtilis 168 mtrA 60.6 86.2 188 GTP cyclohydrolase I2963 6463 2867471 2868385 915 2964 6464 2869748 2867169 2580 56.0 69.0782 cell division protein FtsH 2965 6465 2870444 2869863 582 gp:AF008931_1 Salmonella typhimurium GP660 51.5 83.0 165 hypoxanthine hprtphosphoribosyltransferase 2966 6466 2871389 2870499 891 sp: YZC5_MYCTUMycobacterium tuberculosis 41.0 66.8 310 cell cycle protein MesJ orcytosine H37Rv Rv3625c deaminase-related protein 2967 6467 28726772871445 1233 sp: DAC_ACTSP Actinomadura sp. R39 dac 27.2 51.4 459D-alanyl-D-alanine carboxypeptidase 2968 6468 2872926 2873399 474 sp:IPYR_ECOLI Escherichia coli K12 ppa 49.7 73.6 159 inorganicpyrophosphatase 2969 6469 2873611 2873393 219 2970 6470 2875443 28739051539 pir: H70886 Mycobacterium tuberculosis 56.0 80.7 507 spermidinesynthase H37Rv speE 2971 6471 2875832 2875434 399 sp: Y0B1_MYCTUMycobacterium tuberculosis 38.6 86.4 132 hypothetical membrane proteinH37Rv Rv2600 2972 6472 2876280 2875870 411 sp: Y0B2_MYCTU Mycobacteriumtuberculosis 36.8 63.2 144 hypothetical protein H37Rv Rv2599 2973 64732876777 2876280 498 sp: Y0B3_MYCTU Mycobacterium tuberculosis 36.4 60.1173 hypothetical protein H37Rv Rv2598 2974 6474 2877385 2876777 609 sp:Y0B4_MYCTU Mycobacterium tuberculosis 44.6 72.3 202 hypothetical proteinH37Rv Rv2597 2975 6475 2877703 2877455 249 sp: PTBA_BACSU Bacillussubtilis 168 bgIP 30.3 59.6 89 PTS system, beta-glucosides- permease IIABC component 2976 6476 2877858 2877595 264 2977 6477 2879710 28784781233 gp: AB017795_2 Nocardioides sp. KP7 phdD 38.0 69.6 411 ferredoxinreductase 2978 6478 2879965 2880252 288 gp: SCH69_9 Streptomycescoelicolor A3(2) 46.4 73.2 97 hypothetical protein SCH69.09c 2979 64792880544 2880987 444 prf: 2516298U Burkholderia pseudomallei ORFE 26.759.3 135 bacterial regulatory protein, marR family 2980 6480 28809982884882 3885 prf: 2413335A Streptomyces roseosporus cpsB 28.4 51.6 1241peptide synthase 2981 6481 2883304 2881844 1461 2982 6482 28864972884935 1563 prf: 2310295A Escherichia coli K12 padA 35.0 63.7 488phenylacetaldehyde dehydrogenase 2983 6483 2887833 2886916 918 gp:CJ11168X2_254 Campylobacter jejuni Cj0604 57.3 79.7 241 hypotheticalprotein 2984 6484 2890185 2890346 162 GP: MSGTCWPA_1 Mycobacteriumtuberculosis 62.0 63.0 54 hypothetical protein 2985 6485 2890377 2890553177 GP: MSGTCWPA_1 Mycobacterium tuberculosis 74.0 80.0 31 hypotheticalprotein 2986 6486 2890540 2888897 1644 gsp: R94368 Brevibacterium flavumMJ-233 99.5 100.0 548 heat shock protein or chaperon or groEL protein2987 6487 2890930 2890751 180 2988 6488 2892138 2890930 1209 2989 64892893100 2892138 963 2990 6490 2895085 2893100 1986 2991 6491 28975252895072 2454 2992 6492 2900326 2897528 2799 2993 6493 2903920 29003303591 prf: 2309326A Homo sapiens MUC5B 21.7 42.3 1236 hypotheticalprotein 2994 6494 2906738 2903964 2775 2995 6495 2907250 2906639 6122996 6496 2907515 2908885 1371 pir: G70870 Mycobacterium tuberculosis37.1 68.0 447 peptidase H37Rv Rv2522c 2997 6497 2909210 2909788 579 29986498 2909830 2909231 600 2999 6499 2910172 2913228 3057 prf: 2504285BStaphylococcus aureus mnhA 35.6 68.3 797 Na+/H+ antiporter or multipleresistance and pH regulation related protein A or NADH dehydrogenase3000 6500 2913235 2913723 489 gp: AF097740_3 Bacillus firmus OF4 mrpC44.2 81.7 104 Na+/H+ antiporter or multiple resistance and pH regulationrelated protein C or cation transport system protein 3001 6501 29137492915416 1668 gp: AF097740_4 Bacillus firmus OF4 mrpD 35.2 72.1 523Na+/H+ antiporter or multiple resistance and pH regulation relatedprotein D 3002 6502 2915482 2915922 441 gp: AF097740_5 Bacillus firmusOF4 mrpE 26.7 60.9 161 Na+/H+ antiporter or multiple resistance and pHregulation related protein E 3003 6503 2915929 2916201 273 prf: 2416476GRhizobium meliloti phaF 32.5 66.2 77 K+ efflux system or multipleresistance and pH regulation related protein F 3004 6504 2916205 2916582378 prf: 2504285H Staphylococcus aureus mnhG 25.6 63.6 121 Na+/H+antiporter or multiple resistance and pH regulation related protein G3005 6505 2917617 2917024 594 pir: D70594 Mycobacterium tuberculosis24.7 54.5 178 hypothetical protein H37Rv lipV 3006 6506 2918757 29176301128 sp: YBDK_ECOLI Escherichia coli K12 ybdK 27.0 61.7 334 hypotheticalprotein 3007 6507 2919481 2918819 663 3008 6508 2919715 2920293 579 sp:DEF_BACSU Bacillus subtilis 168 def 37.5 60.9 184 polypeptidedeformylase 3009 6509 2919741 2919490 252 pir: D70631 Mycobacteriumtuberculosis 47.9 70.4 71 hypothetical protein H37Rv Rv0430 3010 65102920286 2921290 1005 pir: B70631 Mycobacterium tuberculosis 31.3 54.2339 acetyltransferase (GNAT) family or H37Rv Rv0428c N terminalacetylating enzyme 3011 6511 2920476 2919808 669 3012 6512 29208492920220 630 3013 6513 2921320 2922108 789 gp: AF108767_1 Salmonellatyphimurium LT2 30.8 59.9 31 exodeoxyrlbonuclease III or xthAexonuclease 3014 6514 2922118 2923617 1500 gp: BFU88888_2 Bacillusfirmus OF4 cls 27.9 62.0 513 cardiolipin synthase 3015 6515 29241912924844 654 3016 6516 2925147 2923954 1194 sp: BCR_ECOLI Escherichiacoli K12 bcr 31.6 67.2 393 membrane transport protein or bicyclomycinresistance protein 3017 6517 2925541 2926704 1164 gp: VCAJ10968_1 Vibriocholerae JS1569 nptA 28.5 68.9 382 sodium dependent phosphate pump 30186518 2927546 2926707 840 sp: PHZC_PSEAR Pseudomonas aureofaciens 30-8438.8 56.4 289 phenazine biosynthesis protein phzC 3019 6519 29282832927651 633 3020 6520 2928318 2927551 768 gp: SCE8_16 Streptomycescoelicolor A3(2) 24.3 60.8 255 ABC transporter SCE8.16c 3021 65212929237 2928302 936 sp: BCRA_BACLI Bacillus licheniformis ATCC 36.9 66.3309 ABC transporter ATP-binding protein 9945A bcrA 3022 6522 29297562929256 501 pir: C70629 Mycobacterium tuberculosis 47.6 68.5 168 mutatormutT protein H37Rv Rv0413 3023 6523 2929951 2931336 1386 pir: B70629Mycobacterium tuberculosis 35.0 70.2 423 hypothetical membrane proteinH37Rv Rv0412c 3024 6524 2931340 2932371 1032 sp: GLNH_BACST Bacillusstearothermophilus 31.5 64.8 270 glutamine-binding protein precursorNUB36 glnH 3025 6525 2932577 2934829 2253 plr: H70628 Mycobacteriumtuberculosis 41.2 63.5 805 serine/threonine kinase H37Rv Rv0410c pknG3026 6526 2933398 2932652 747 3027 6527 2938403 2939767 1365 sp:ADRO_BOVIN Bos taurus 37.2 67.8 457 ferredoxin/ferredoxin-NADP reductase3028 6528 2939907 2940452 546 sp: ELAA_ECOLI Escherichia coli K12 elaA34.0 60.3 156 acetyltransferase (GNAT) family 3029 6529 2941508 29404471062 3030 6530 2942500 2941472 1029 3031 6531 2943007 2942609 399 30326532 2944205 2943012 1194 sp: PURT_BACSU Bacillus subtills 168 purT 59.182.6 379 phosphoribosylglycinamide formyltransferase 3033 6533 29465262945639 888 3034 6534 2947591 2946698 894 pir: S60890 Corynebacteriumglutamicum 77.6 90.9 295 insertion element (IS3 related) orf2 3035 65352947886 2947620 267 pir: S60889 Corynebacterium glutamicum 67.4 84.3 89insertion element (IS3 related) orf1 3036 6536 2949188 2948049 1140 gp:AB016841_1 Streptomyces thermoviolaceus 22.4 51.3 349 two-componentsystem sensor opc-520 chiS histidine kinase 3037 6537 2949882 2949265618 sp: DEGU_BACBR Bacillus brevis ALK36 degU 31.7 65.6 218transcriptional regulator 3038 6538 2950207 2950431 225 3039 65392951723 2950434 1290 gp: AB003160_1 Corynebacterium 89.7 95.3 427adenylosuccinate synthetase ammoniagenes purA 3040 6540 2951933 2952691759 pir: G70575 Mycobacterium tuberculosis 34.3 59.3 204 hypotheticalprotein H37Rv Rv0358 3041 6541 2952709 2952972 264 3042 6542 29541412952975 1167 sp: YFDA_CORGL Corynebacterium glutamicum 100.0 100.0 359hypothetical membrane protein AS019 ATCC 13059 ORF3 3043 6543 29552722954241 1032 pir: S09283 Corynebacterium glutamicum 99.7 100.0 344fructose-bisphosphate aldolase AS019 ATCC 13059 fda 3044 6544 29564732955523 951 gp: CGFDA_1 Corynebacterium glutamicum 100.0 100.0 304hypothetical protein AS019 ATCC 13059 ORF1 3045 6545 2957447 2956830 618pir: G70833 Mycobacterium tuberculosis 76.9 91.2 182 methyltransferaseH37Rv Rv0380c 3046 6546 2958036 2957485 552 gp: AF058713_1 Pyrococcusabyssi pyrE 39.1 65.5 174 orotate phosphoribosyltransferase 3047 65472959110 2958139 972 pir: B70834 Mycobacterium tuberculosis 27.6 60.0 250hypothetical protein H37Rv Rv0383c 3048 6548 2960371 2959520 852 sp:THTM_HUMAN Homo sapiens mpsT 29.6 56.1 294 3-mercaptopyruvatesulfurtransferase 3049 6549 2961187 2960468 720 3050 6550 29630082962730 279 3051 6551 2963596 2963198 399 3052 6552 2964258 2964434 177GSP: Y29188 Pseudomonas aeruginosa 76.0 82.0 59 virulence factorORF24222 3053 6553 2965076 2965837 762 GSP: Y29182 Pseudomonasaeruginosa 38.0 55.0 200 virulence factor ORF23228 3054 6554 29651882965583 396 GSP: Y29193 Pseudomonas aeruginosa 62.0 63.0 132 virulencefactor ORF25110 3055 6555 2967804 2966458 1347 pir: S76683 Synechocystissp. PCC6803 24.7 54.8 489 sodium/glutamate symport carrier slr0625protein 3056 6556 2968403 2968789 387 sp: CADF_STAAU Staphylococcusaureus cadC 37.0 71.3 108 cadmium resistance protein 3057 6557 29689512969808 858 pir: H75109 Pyrococcus abyssi Orsay 23.7 63.3 283 cationefflux system protein PAB0462 (zinc/cadmium) 3058 6558 2969834 29710031170 gp: AB010439_1 Rhodococcus rhodochrous 22.5 45.4 476 monooxygenaseor oxidoreductase IFO3338 or steroid monooxygenase 3059 6559 29710172972057 1041 sp: LUXA_KRYAS Kryptophanaron alfredi symbiont 21.1 47.4399 alkanal monooxygenase alpha chain luxA 3060 6560 2972099 2971338 7623061 6561 2973205 2972060 1146 sp: METB_ECOLI Escherichia coli K12 metB36.5 62.4 375 cystathionine gamma-lyase 3062 6562 2973796 2973230 567gp: SC1A2_11 Streptomyces coelicolor A3(2) 40.2 67.9 184 bacterialregulatory protein, lacl SC1A2.11 family 3063 6563 2973961 2974200 240gp: SCE20_34 Streptomyces coelicolor A3(2) 49.4 65.2 89 rifampinADP-ribosyl transferase SCE20.34c arr 3064 6564 2974200 2974382 183 gp:SCE20_34 Streptomyces coelicolor A3(2) 73.2 87.5 56 rifampin ADP-ribosyltransferase SCE20.34c arr 3065 6565 2974467 2975591 1125 pir: E70812Mycobacterium tuberculosis 30.5 56.2 361 hypothetical protein H37RvRv0837c 3066 6566 2975629 2976360 732 pir: D70812 Mycobacteriumtuberculosis 33.8 64.7 204 hypothetical protein H37Rv Rv0836c 3067 65672976596 2977774 1179 pir: D70834 Mycobacterium tuberculosis 31.9 60.6386 oxidoreductase H37Rv Rv0385 3068 6568 2978644 2977847 798 pir:B69109 Methanobacterium 32.0 67.3 275 N-carbamoyl-D-amino acidthermoautotrophicum Delta H amidohydrolase MTH1811 3069 6569 29787372978979 243 3070 6570 2978982 2980115 1134 gp: SC4A7_3 Streptomycescoelicolor A3(2) 28.0 55.4 289 hypothetical protein SC4A7.03 3071 65712980887 2981216 330 GP: ABCARRA_2 Azospirillum brasilense carR 38.0 44.0108 novel two-component regulatory system 3072 6572 2981698 2980181 1518prf: 2104333D Rhodococcus erythropolis thcA 69.6 90.3 507 aldehydedehydrogenase 3073 6573 2982460 2982023 438 gp: SAU43299_2 Streptomycesalbus G hspR 47.4 70.4 135 heat shock transcription regulator 3074 65742983679 2982495 1185 sp: DNAJ_MYCTU Mycobacterium tuberculosis 56.7 80.1397 heat shock protein dnaJ H37Rv RV0352 dnaJ 3075 6575 2984522 2983887636 sp: GRPE_STRCO Streptomyces coelicolor grpE 38.7 66.5 212 nucleotideexchange factor grpE protein bound to the ATPase domain of the molecularchaperone DnaK 3076 6576 2986397 2984544 1854 gsp: R94587 Brevibacteriumflavum MJ-233 99.8 99.8 618 heat shock protein dnaK dnaK 3077 65772986833 2988164 1332 gp: SCF6_8 Streptomyces coelicolor A3(2) 42.6 79.0338 hypothetical membrane protein SCF6.09 3078 6578 2988846 2988214 633sp: PFS_HELPY Helicobacter pylori HP0089 mtn 27.2 60.0 1955′-methylthioadenosine nucleosidase and S- adenosylhomocysteinenucleosidase 3079 6579 2990045 2988846 1200 3080 6580 2991718 2992602885 3081 6581 2993286 2989954 3333 sp: CUT3_SCHPO Schizosaccharomycespombe 18.9 48.4 1311 chromosome segregation protein cut3 3082 65822993921 2993286 636 3083 6583 2995405 2993921 1485 3084 6584 29967812995747 1035 sp: ADH2_BACST Bacillus stearothermophilus 50.0 81.7 334alcohol dehydrogenase DSM 2334 adh 3085 6585 2997151 2997366 216 30866586 2997687 2997481 207 3087 6587 2997688 2997876 189 3088 6588 29982232997963 261 3089 6589 2999454 2998528 927 pir: F69997 Bacillus subtilisytnM 43.5 70.1 301 hypothetical membrane protein 3090 6590 30002002999478 723 gp: SC7A8_10 Streptomyces coelicolor A3(2) 32.5 53.2 252hypothetical protein SC7A8.10c 3091 6591 3001512 3002426 915 3092 65923001539 3000241 1299 sp: CYSN_ECOLI Escherichia coli K12 cysN 47.3 78.3414 sulfate adenylyltransferase, subunit 1 3093 6593 3002453 3001542 912sp: CYSD_ECOLI Escherichia coli K12 cysD 46.1 70.1 308 sulfateadenylyltransferase small chain 3094 6594 3003145 3002453 693 sp:CYH1_BACSU Bacillus subtilis cysH 39.2 64.2 212 phosphoadenosinephosphosulfate reductase 3095 6595 3005162 3003480 1683 sp: NIR_SYNP7Synechococcus sp. PCC 7942 34.5 65.5 502 ferredoxin—nitrate reductase3096 6596 3005545 3006915 1371 sp: ADRO_YEAST Saccharomyces cerevisiae30.8 61.4 487 ferredoxin/ferredoxin-NADP FL200 arh1 reductase 3097 65973007294 3008376 1083 prf: 2420294J Homo sapiens hypE 32.6 59.7 144huntingtin interactor 3098 6598 3008689 3008453 237 3099 6599 30087703009303 534 3100 6600 3009162 3008749 414 sp: PHNB_ECOLI Escherichiacoli K12 phnB 26.8 59.9 142 alkylphosphonate uptake protein and C-Plyase activity 3101 6601 3009242 3009607 366 gp: SCE68_10 Streptomycescoelicolor A3(2) 50.0 66.3 80 hypothetical protein SCE68.10 3102 66023010231 3009710 522 gp: PPAMOA_1 Pseudomonas putida DSMZ ID 39.1 76.4161 ammonia monooxygenase 88-260 amoA 3103 6603 3010659 3010979 321 31046604 3010926 3010441 486 3105 6605 3010989 3011273 285 SP: YTZ3_AGRVIAgrobacterium vitis ORFZ3 41.0 58.0 68 hypothetical protein 3106 66063011805 3011242 564 3107 6607 3012809 3011808 1002 sp: YGB7_ALCEUAlcaligenes eutrophus H16 26.1 57.9 337 hypothetical protein ORF7 31086608 3013798 3013106 693 gp: HIU68399_3 Haemophilus influenzae hmcB 35.764.8 199 ABC transporter 3109 6609 3014550 3013837 714 gp: HIU68399_3Haemophilus influenzae hmcB 39.3 73.0 211 ABC transporter 3110 66103014616 3015824 1209 pir: A69778 Bacillus subtilis ydeG 30.8 67.8 416metabolite transport protein homolog 3111 6611 3015469 3014648 822 31126612 3016238 3016924 687 3113 6613 3017149 3015827 1323 sp: DAPE_ECOLIEscherichia coli K12 msgB 21.5 48.5 466 succinyl-diaminopimelatedesuccinylase 3114 6614 3017316 3019220 1905 3115 6615 3017539 3018312774 3116 6616 3018181 3017420 762 3117 6617 3019076 3018123 954 GPU:DCA297422_1 Daucus carota 33.0 46.0 114 dehydrin-like protein 3118 66183020609 3019542 1068 sp: MALK_ECOLI Escherichia coli K12 malK 24.9 50.1373 maltose/maltodextrin transport ATP- binding protein 3119 66193021202 3020561 642 3120 6620 3021825 3021208 618 gp: AF036485_6Lactococcus lactis Plasmid 30.2 67.6 179 cobalt transport proteinpNZ4000 Orf-200 cbiM 3121 6621 3022928 3022113 816 sp: FRP_VIBHA Vibrioharveyi MAV frp 37.2 71.4 231 NADPH-flavin oxidoreductase 3122 66223023900 3022998 903 sp: IUNH_CRIFA Crithidia fasciculata iunH 28.4 59.3317 inosine-uridine preferring nucleoside hydrolase 3123 6623 30243793025353 975 gp: SCE20_8 Streptomyces coelicolor A3(2) 31.2 59.4 276hypothetical membrane protein SCE20.08c 3124 6624 3025552 3026139 588sp: 3MG1_ECOLI Escherichia coli K12 tag 50.3 78.8 179DNA-3-methyladenine glycosylase 3125 6625 3027299 3026142 1158 sp:HMPA_ALCEU Alcaligenes eutrophus H16 fhp 33.5 63.8 406 flavohemoprotein3126 6626 3027561 3028163 603 3127 6627 3028268 3028891 624 gp:SCO276673_18 Streptomyces coelicolor A3(2) 34.8 63.8 210 oxidoreductasemmyQ 3128 6628 3028878 3029033 156 3129 6629 3029474 3028884 591 sp:BGLG_ECOLI Escherichia coli K12 bglC 28.1 69.3 192 transcriptionantiterminator or beta- glucoside positive regulatory protein 3130 66303029504 3029782 279 3131 6631 3030061 3029702 360 sp: ABGA_CLOLOClostridium longisporum B6405 43.7 59.9 167 6-phospho-beta-glucosidaseabgA 3132 6632 3030155 3030535 381 3133 6633 3030340 3030101 240 sp:ABGA_CLOLO Clostridium longisporum B6405 43.9 78.8 666-phospho-beta-glucosidase abgA 3134 6634 3030723 3031979 1257 gp:L78665_2 Methylobacillus flagellatus aat 53.7 80.9 402 aspartateaminotransferase 3135 6635 3032647 3032348 300 3136 6636 3032661 30338631203 gp: AF189147_1 Corynebacterium glutamicum 100.0 100.0 401transposase (ISCg2) ATCC 13032 tnp 3137 6637 3034181 3035437 1257 gp:SCQ11_10 Streptomyces coelicolor A3(2) 33.6 70.2 399 hypotheticalmembrane protein SCQ11.10c 3138 6638 3034287 3034105 183 3139 66393036756 3035440 1317 prf: 2422381B SinoRhizobium meliloti rkpK 40.5 72.2442 UDP-glucose dehydrogenase 3140 6640 3037411 3036845 567 sp:DCD_ECOLI Escherichia coli K12 dcd 43.6 72.3 188 deoxycytidinetriphosphate deaminase 3141 6641 3037675 3037911 237 3142 6642 30381723038942 771 gp: SCC75A_16 Streptomyces coelicolor A3(2) 30.6 59.4 229hypothetical protein SCC75A.16c 3143 6643 3040681 3038993 1689 3144 66443041932 3040748 1185 gp: AB008771_1 Streptomyces thermoviolaceus 28.558.1 410 beta-N-Acetylglucosaminidase nagA 3145 6645 3041994 3042437 4443146 6646 3042503 3042703 201 3147 6647 3042660 3045788 3129 gp:MLCB1883_7 Mycobacterium leprae 29.6 49.4 1416 hypothetical proteinMLCB1883.13c 3148 6648 3043642 3043022 621 3149 6649 3045796 3045990 1953150 6650 3047146 3048048 903 gp: MLCB1883_4 Mycobacterium leprae 24.847.1 363 hypothetical membrane protein MLCB1883.05c 3151 6651 30471893046122 1068 pir: JC4001 Streptomyces sp. acyA 27.7 51.0 408acyltransferase or macrolide 3-O- acyltransferase 3152 6652 30479043047197 708 3153 6653 3048058 3049479 1422 gp: MLCB1883_3 Mycobacteriumleprae 31.2 54.8 529 hypothetical membrane protein MLCB1883.04c 31546654 3050522 3051190 669 3155 6655 3050592 3049456 1137 pir: G70961Mycobacterium tuberculosis 53.4 79.1 369 hexosyltransferase H37Rv Rv02253156 6656 3051194 3051964 771 pir: F70961 Mycobacterium tuberculosis58.6 73.3 251 methyl transferase H37Rv Rv0224c 3157 6657 3053891 30520621830 sp: PPCK_NEOFR Neocallimastix frontalis pepck 54.7 78.5 601phosphoenolpyruvate carboxykinase (GTP) 3158 6658 3054759 3055769 1011pir: E75125 Pyrococcus abyssi Orsay 24.4 52.7 332 C4-dicarboxylatetransporter PAB2393 3159 6659 3055867 3056631 765 sp: YGGH_ECOLIEscherichia coli K12 yggH 35.7 67.2 241 hypothetical protein 3160 66603056613 3057317 705 pir: E70959 Mycobacterium tuberculosis 69.1 85.0 207hypothetical protein H37Rv Rv0207c 3161 6661 3057328 3059643 2316 pir:C70839 Mycobacterium tuberculosis 42.3 72.3 768 mebrane transportprotein H37Rv Rv0206c mmpL3 3162 6662 3059517 3058096 1422 3163 66633059651 3060733 1083 pir: A70839 Mycobacterium tuberculosis 29.1 62.9364 hypothetical membrane protein H37Rv Rv0204c 3164 6664 30607333061095 363 pir: H70633 Mycobacterium tuberculosis 34.3 69.4 108hypothetical membrane protein H37Rv Rv0401 3165 6665 3062927 30613801548 gp: AF113605_1 Streptomyces coelicolor A3(2) 49.7 76.9 523propionyl-CoA carboxylase complex pccB B subunit 3166 6666 30677803062951 4830 sp: ERY1_SACER Streptomyces erythraeus eryA 30.2 54.2 1747polyketide synthase 3167 6667 3069930 3068143 1788 prf: 2310345AMycobacterium bovis BCG 33.5 62.3 592 acyl-CoA synthase 3168 66683071140 3070214 927 pir: F70887 Mycobacterium tuberculosis 39.8 67.4 319hypothetical protein H37Rv Rv3802c 3169 6669 3071644 3071147 498 31706670 3073620 3071650 1971 sp: CSP1_CORGL Corynebacterium glutamicum 98.699.5 657 major secreted protein PS1 protein (Brevibacterium flavum) ATCCprecursor 17965 cop1 3171 6671 3074047 3075447 1401 3172 6672 30740753073857 219 3173 6673 3076562 3075540 1023 sp: A85C_MYCTU Mycobacteriumtuberculosis 36.3 62.5 331 antigen 85-C ERDMANN RV0129C fbpC 3174 66743078772 3076715 2058 pir: A70888 Mycobacterium tuberculosis 37.5 61.2667 hypothetical membrane protein H37Rv Rv3805c 3175 6675 30798483078853 996 sp: NOEC_AZOCA Azorhizobium caulinodans 27.1 51.5 295nodulation protein ORS571 noeC 3176 6676 3080351 3079848 504 pir: C70888Mycobacterium tuberculosis 51.2 75.0 168 hypothetical protein H37RvRv3807c 3177 6677 3082311 3080344 1968 pir: D70888 Mycobacteriumtuberculosis 55.6 74.7 656 hypothetical protein H37Rv Rv3808c 3178 66783082467 3083960 1494 3179 6679 3084411 3083935 477 sp: BCRC_BACLIBacillus licheniformis ATCC 28.2 56.5 170 phosphatidic acid phosphatase9945A bcrC 3180 6680 3085200 3084424 777 3181 6681 3085727 3085218 5103182 6682 3085747 3087048 1302 sp: FMO1_PIG Sus scrofa fmo1 24.4 50.4377 dimethylaniline monooxygenase (N- oxide-forming) 3183 6683 30876653088276 612 3184 6684 3088303 3087101 1203 sp: GLF_ECOLI Escherichiacoli K12 glf 43.2 72.9 377 UDP-galactopyranose mutase 3185 6685 30886163090664 2049 pir: G70520 Mycobacterium tuberculosis 29.6 47.8 659hypothetical protein H37Rv Rv3811 csp 3186 6686 3092286 3090760 1527 sp:GLPK_PSEAE Pseudomonas aeruginosa 51.7 78.8 499 glycerol kinase ATCC15692 glpK 3187 6687 3093175 3092342 834 pir: A70521 Mycobacteriumtuberculosis 41.6 70.3 279 hypothetical protein H37Rv Rv3813c 3188 66883094050 3093175 876 pir: D70521 Mycobacterium tuberculosis 46.7 72.0 261acyltransferase H37Rv Rv3816c 3189 6689 3095343 3094078 1266 gsp: W26465Mycobacterium tuberculosis 70.2 87.6 419 seryl-tRNA synthetase H37Rv3190 6690 3095574 3096287 714 sp: FARR_ECOLI Escherichia coli K12 farR27.7 61.7 235 transcriptional regulator, GntR family or fattyacyl-responsive regulator 3191 6691 3096311 3097423 1113 pir: H70652Mycobacterium tuberculosis 32.6 61.2 356 hypothetical protein H37RvRv3835 3192 6692 3097423 3097764 342 pir: A70653 Mycobacteriumtuberculosis 46.0 79.7 113 hypothetical protein H37Rv Rv3836 3193 66933097878 3097780 99 3194 6694 3098572 3097904 669 gp: AMU73808_1Amycolatopsis methanolica pgm 37.2 62.8 218 2,3-PDG dependentphosphoglycerate mutase 3195 6695 3098825 3099454 630 3196 6696 30995563100698 1143 prf: 2501285A Mycobacterium smegmatis pzaA 27.4 50.9 460nicotinamidase or pyrazinamidase 3197 6697 3100698 3101426 729 3198 66983101734 3102768 1035 gp: SC6G4_33 Streptomyces coelicolor A3(2) 31.657.1 380 transcriptional regulator SC6G4.33 3199 6699 3101863 3101744120 3200 6700 3102630 3102079 552 3201 6701 3102894 3103763 870 32026702 3103926 3104252 327 pir: B26872 Streptomyces lavendulae 43.9 81.3107 hypothetical protein ORF372 3203 6703 3104406 3105719 1314 sp:AMYH_YEAST Saccharomyces cerevisiae 28.7 55.3 432 glucan1,4-alpha-glucosidase S288C YIR019C sta1 3204 6704 3106970 3106053 9183205 6705 3107769 3106951 819 sp: GLPQ_BACSU Bacillus subtilis glpQ 29.054.1 259 glycerophosphoryl diester phosphodiesterase 3206 6706 31081313109519 1389 sp: GNTP_BACSU Bacillus subtilis gntP 37.3 71.9 456gluconate permease 3207 6707 3109464 3108823 642 3208 6708 31098453110003 159 3209 6709 3112080 3110464 1617 sp: KPYK_CORGLCorynebacterium glutamicum 25.5 47.7 491 pyruvate kinase AS019 pyk 32106710 3113390 3112449 942 gsp: Y25997 Brevibacterium flavum lctA 99.799.7 314 L-lactate dehydrogenase 3211 6711 3113619 3115394 1776 pir:C70893 Mycobacterium tuberculosis 33.5 64.8 526 hypothetical proteinH37Rv Rv1069c 3212 6712 3115407 3116042 636 gp: SC1C2_30 Streptomycescoelicolor A3(2) 32.1 58.5 224 hydrolase or haloacid SC1C2.30dehalogenase-like hydrolase 3213 6713 3116079 3116621 543 gp: AF030288_1Brevibacterium linens ORF1 39.9 67.6 188 efflux protein tmpA 3214 67143116640 3117332 693 sp: GLCC_ECOLI Escherichia coli K12 MG1655 27.6 57.0221 transcription activator or glcC transcriptional regulator GntRfamily 3215 6715 3117336 3118121 786 pir: B70885 Mycobacteriumtuberculosis 47.8 68.6 255 phosphoesterase H37Rv Rv2795c 3216 67163118284 3119582 1299 sp: SHIA_ECOLI Escherichia coli K12 shiA 37.9 74.4422 shikimate transport protein 3217 6717 3119665 3120879 1215 prf:2219306A Neisseria meningitidis lldA 40.4 68.9 376 L-lactatedehydrogenase or FMN- dependent dehydrogenase 3218 6718 3120909 3121313405 3219 6719 3121598 3121909 312 sp: RPC_BPPH1 Bacillus phage phi-105ORF1 45.5 80.0 55 immunity repressor protein 3220 6720 3122129 3121992138 3221 6721 3123222 3123932 711 3222 6722 3124172 3122556 1617 gp:CELY51B11A_1 Caenorhabditis elegans 29.5 51.3 569 phosphatase or reverseY51B11A.1 transcriptase (RNA-dependent) 3223 6723 3124886 3124341 5463224 6724 3125298 3124897 402 sp: ILL1_ARATH Arabidopsis thaliana ill136.9 63.1 122 peptidase or IAA-amino acid hydrolase 3225 6725 31253433125492 150 3226 6726 3126145 3125495 651 sp: PMSR_ECOLI Escherichiacoli B msrA 47.6 69.1 210 peptide methionine sulfoxide reductase 32276727 3126392 3126991 600 pir: I40858 Corynebacterium 82.3 92.7 164superoxide dismutase (Fe/Mn) pseudodiphtheriticum sod 3228 6728 31284173127494 924 sp: GLTC_BACSU Bacillus subtilis gltC 32.5 65.8 292transcriptional regulator 3229 6729 3128606 3129739 1134 gp: AF121000_10Corynebacterium glutamicum 23.4 49.0 384 multidrug resistancetransporter tetA 3230 6730 3129785 3131395 1611 3231 6731 31329203133030 111 3232 6732 3133028 3131508 1521 3233 6733 3133115 3133747 633pir: G70654 Mycobacterium tuberculosis 33.8 64.8 216 hypotheticalprotein H37Rv Rv3850 3234 6734 3135268 3133778 1491 prf: 2508244ABStreptomyces cyanogenus lanJ 27.3 59.3 447 membrane transport protein3235 6735 3135297 3135752 456 sp: YXAD_BACSU Bacillus subtilis 168 yxaD37.2 65.0 137 transcriptional regulator 3236 6736 3136491 3135856 636prf: 2518330B Corynebacterium diphtheriae 50.9 75.5 212 two-componentsystem response chrA regulator 3237 6737 3136920 3137558 639 3238 67383137884 3138471 588 3239 6739 3137903 3136593 1311 prf: 2518330ACorynebacterium diphtheriae 30.2 64.5 408 two-component system sensorchrS histidine kinase 3240 6740 3138630 3138481 150 gp: SCH69_22Streptomyces coelicolor A3(2) 45.8 79.2 48 hypothetical proteinSCH69.22c 3241 6741 3139455 3138634 822 gp: SCH69_20 Streptomycescoelicolor A3(2) 30.0 59.2 277 hypothetical protein SCH69.20c 3242 67423139651 3140952 1302 sp: SP3J_BACSU Bacillus subtilis spolllJ 26.0 53.6265 stage III sporulation protein 3243 6743 3141523 3140885 639 pir:C70948 Mycobacterium tuberculosis 32.3 60.9 192 transcriptionalrepressor H37Rv Rv3173c 3244 6744 3141969 3141709 261 sp: TAG1_ECOLIEscherichia coli K12.MG1655 34.5 71.3 87 transglycosylase-associatedprotein tag 1 3245 6745 3143356 3142454 903 sp: YW12_MYCTU Mycobacteriumtuberculosis 41.2 69.6 296 hypothetical protein H37Rv Rv2005c 3246 67463144482 3143496 987 sp: YHBW_ECOLI Escherichia coli K12 MG1655 38.5 73.9314 hypothetical protein yhbW 3247 6747 3144661 3145626 966 sp:YBC5_CHLVI Chlorobium vibrioforme ybc5 28.4 51.2 334 RNA pseudouridylatesynthase 3248 6748 3146569 3146841 273 GSP: Y35814 Chlamydia pneumoniae61.0 66.0 84 hypothetical protein 3249 6749 3147090 3147230 141 PIR:F81737 Chlamydia muridarum Nigg 71.0 75.0 42 hypothetical protein TC01293250 6750 3151575 3151369 207 3251 6751 3152204 3151842 363 sp:GLCC_ECOLI Escherichia coli K12 MG1655 30.3 56.0 109 bacterialregulatory protein, gntR glcC family or glc operon transcriptionalactivator 3252 6752 3152413 3153828 1416 gp: SC4G6_31 Streptomycescoelicolor 26.0 48.2 488 hypothetical protein SC4G6.31c 3253 67533154766 3153894 873 sp: 35KD_MYCTU Mycobacterium tuberculosis 48.3 78.7267 hypothetical protein H37Rv Rv2744c 3254 6754 3154817 3154969 1533255 6755 3156697 3155246 1452 3256 6756 3157373 3156306 1068 3257 67573157471 3157223 249 3258 6758 3157787 3157479 309 3259 6759 31581243158834 711 gp: SCD35_11 Streptomyces coelicolor A3(2) 32.3 58.1 217methyltransferase SCD35.11c 3260 6760 3159800 3159081 720 sp: NO21_SOYBNsoybean NO21 26.1 55.2 241 nodulin 21-related protein 3261 6761 31602163160419 204 3262 6762 3160688 3161065 378 3263 6763 3160816 3161001 1863264 6764 3160938 3160723 216 sp: TNP5_PSEAE Pseudomonas aeruginosa TNP548.2 92.9 56 transposon tn501 resolvase 3265 6765 3161219 3161701 4833266 6766 3161407 3161087 321 sp: FER_SACER Saccharopolyspora erythraeafer 90.3 98.4 62 ferredoxin precursor 3267 6767 3162014 3161682 333 gp:SCD31_14 Streptomyces coelicolor A3(2) 47.3 85.5 55 hypothetical protein3268 6768 3162694 3162804 111 GPU: AF164956_8 Corynebacterium glutamicum81.0 84.0 27 transposase Tnp1673 3269 6769 3162710 3162871 162 GPU:AF164956_23 Corynebacterium glutamicum 84.0 90.0 46 transposase proteinfragment TnpNC 3270 6770 3162852 3163889 1038 3271 6771 3162983 3162858126 sp: G3P_PYRWO Pyrococcus woesei gap 63.2 84.2 38glyceraldehyde-3-phosphate dehydrogenase (pseudogene) 3272 6772 31637333163074 660 pir: S77018 Synechocystis sp. PCC6803 32.2 59.4 180lipoprotein sll0788 3273 6773 3166005 3163789 2217 pir: H69268Archaeoglobus fulgidus AF0152 45.8 73.4 717copper/potassium-transporting ATPase B or cation transporting ATPase(E1-E2 family) 3274 6774 3166437 3166267 171 3275 6775 3166978 3167169192 3276 6776 3167646 3166450 1197 sp: BAES_ECOLI Escherichia coli K12baeS 37.5 71.4 301 two-component system sensor histidine kinase 32776777 3167739 3168566 828 3278 6778 3168401 3167646 756 sp: PHOP_BACSUBacillus subtilis phoP 43.4 72.1 233 two-component response regulator oralkaline phosphatase synthesis transcriptional regulatory protein 32796779 3168669 3169340 672 3280 6780 3169414 3170892 1479 sp: COPA_PSESMPseudomonas syringae pv. 26.7 47.9 630 laccase or copper resistanceprotein tomato copA precursor A 3281 6781 3171254 3171616 363 sp:TLPA_BRAJA Bradyrhizobium japonicum tlpA 31.7 63.4 101 thiol: disulfideinterchange protein (cytochrome c biogenesis protein) 3282 6782 31725363171619 918 sp: QOR_MOUSE Mus musculus qor 31.4 60.9 322 quinoneoxidoreductase (NADPH: quinone reductase)(seta- crystallin) 3283 67833172995 3173465 471 3284 6784 3173624 3173857 234 sp: ATZN_SYNY3Synechocystis sp. PCC6803 37.2 66.7 78 zinc-transporting ATPase (Zn(II)-atzN translocating p-type ATPase 3285 6785 3174066 3174380 315 3286 67863174990 3174784 207 3287 6787 3175027 3176901 1875 sp: ATZN_ECOLIEscherichia coli K12 MG1655 39.8 68.5 606 zinc-transporting ATPase(Zn(II)- atzN translocating p-type ATPase 3288 6788 3175643 3175254 390PIR: E72491 Aeropyrum pernix K1 APE2572 45.0 54.0 72 hypotheticalprotein 3289 6789 3177174 3177482 309 3290 6790 3177304 3177089 216 GPU:AF164956_8 Corynebacterium glutamicum 58.0 73.0 73 transposase Tnp16733291 6791 3177565 3177308 258 GPU: AF164956_8 Corynebacterium glutamicum75.0 77.0 70 transposase Tnp1673 3292 6792 3177683 3177525 159 gp:AF121000_8 Corynebacterium glutamicum 92.5 96.2 53 transposase (IS1628)22243 R-plasmid pAG1 tnpB 3293 6793 3178558 3178112 447 sp: THI2_ECOLIEscherichia coli K12 thi2 39.0 74.0 100 thioredoxin 3294 6794 31786093178872 264 3295 6795 3179049 3180392 1344 sp: PCAK_PSEPU Pseudomonasputida pcaK 27.1 60.1 421 transmembrane transport protein or4-hydroxybenzoate transporter 3296 6796 3181104 3180946 159 3297 67973181126 3180551 576 sp: YQJI_ECOLI Escherichia coli K12 yqjI 35.1 62.5208 hypothetical protein 3298 6798 3182866 3181337 1530 sp: DNAB_ECOLIEscherichia coli K12 dnaB 37.7 73.1 461 replicative DNA helicase 32996799 3183469 3183984 516 3300 6800 3183927 3183478 450 sp: RL9_ECOLIEscherichia coli K12 RL9 42.2 71.4 154 50S ribosomal protein L9 33016801 3184661 3183987 675 sp: SSB_ECOLI Escherichia coli K12 ssb 30.651.5 229 single-strand DNA binding protein 3302 6802 3184985 3184701 285sp: RS6_ECOLI Escherichia coli K12 RS6 28.3 78.3 92 30S ribosomalprotein S6 3303 6803 3185536 3185348 189 3304 6804 3186993 3185536 1458gp: AF187306_1 Mycobacterium smegmatis 41.5 68.3 480 hypotheticalprotein mc(2)155 3305 6805 3187912 3188793 882 3306 6806 3189201 31870422160 sp: PBPA_BACSU Bacillus subtilis ponA 29.1 60.1 647penicillin-binding protein 3307 6807 3189652 3189296 357 sp: Y0HC_MYCTUMycobacterium tuberculosis 41.1 72.0 107 hypothetical protein H37RvRv0049 3308 6808 3189877 3190347 471 pir: B70912 Mycobacteriumtuberculosis 35.1 65.0 137 bacterial regulatory protein, marR H37RvRv0042c family 3309 6809 3190378 3191319 942 sp: Y0FF_MYCTUMycobacterium tuberculosis 29.7 61.8 296 hypothetical protein H37RvRv2319c yofF 3310 6810 3191354 3191848 495 3311 6811 3192242 3191922 321sp: YHGC_BACSU Bacillus subtilis yhgC 32.4 70.4 71 hypothetical protein3312 6812 3193201 3192266 936 sp: YCEA_ECOLI Escherichia coli K12 yceA30.2 63.8 298 hypothetical protein 3313 6813 3194514 3193252 1263 sp:YBJZ_ECOLI Escherichia coli K12 ybjZ 31.2 64.0 433 ABC transporterATP-binding protein 3314 6814 3195203 3194514 690 sp: YBJZ_ECOLIEscherichia coli K12 MG1655 48.9 80.1 221 ABC transporter ATP-bindingprotein ybjZ 3315 6815 3197186 3195210 1977 pir: E81408 Campylobacterjejuni Cj0606 18.0 42.0 237 hypothetical protein 3316 6816 31974123198500 1089 pir: F70912 Mycobacterium tuberculosis 77.8 90.0 360hypothetical protein H37Rv Rv0046c 3317 6817 3199187 3198582 606 33186818 3200686 3199202 1485 3319 6819 3201754 3201260 495 sp: DPS_ECOLIEscherichia coli K12 dps 37.7 64.9 154 DNA protection during starvationprotein 3320 6820 3201900 3202712 813 sp: FPG_ECOLI Escherichia coli K12mutM or 28.4 55.6 268 formamidopyrimidine-DNA fpg glycosylase 3321 68213202952 3204100 1149 sp: RTCB_ECOLI Escherichia coli K12 rtcB 47.5 66.6404 hypothetical protein 3322 6822 3204067 3202979 1089 3323 68233204156 3204728 573 3324 6824 3205204 3204731 474 sp: MGMT_HUMAN Homosapiens mgmT 38.0 63.3 166 methylated-DNA—protein-cysteineS-methyltransferase 3325 6825 3206232 3205222 1011 sp: QOR_CAVPO Caviaporcellus (Guinea pig) qor 33.3 63.6 231 zinc-binding dehydrogenase orquinone oxidoreductase (NADPH: quinone reductase) or alginate lyase 33266826 3206646 3206756 111 3327 6827 3206849 3208024 1176 sp: YDEA_ECOLIMycobacterium tuberculosis 26.4 66.3 398 membrane transport proteinH37Rv Rv0191 ydeA 3328 6828 3208279 3209454 1176 gp: AF234535_1Corynebacterium melassecola 99.7 99.5 392 malate oxidoreductase [NAD](malic (Corynebacterium glutamicum) enzyme) ATCC 17965 malE 3329 68293211186 3209705 1482 sp: GNTK_BACSU Bacillus subtilis gntK 24.5 53.7 486gluconokinase or gluconate kinase 3330 6830 3211836 3211246 591 sp:VANZ_ENTFC Enterococcus faecium vanZ 27.8 60.4 169 teicoplaninresistance protein 3331 6831 3212428 3211904 525 sp: VANZ_ENTFCEnterococcus faecium vanZ 27.0 159.0 159 teicoplanin resistance protein3332 6832 3212588 3213931 1344 sp: MERA_STAAU Staphylococcus aureus merA29.9 65.6 448 mercury(II) reductase 3333 6833 3215163 3213934 1230 sp:DADA_ECOLI Escherichia coli K12 dadA 27.3 54.5 444 D-amino aciddehydrogenase small subunit 3334 6834 3216759 3215257 1503 3335 68353217215 3216886 330 3336 6836 3217777 3217457 321 3337 6837 32179933218601 609 sp: NOX_THETH Thermus thermophilus nox 25.8 55.2 194 NAD(P)Hnitroreductase 3338 6838 3218777 3219700 924 3339 6839 3221044 32224951452 3340 6840 3222633 3219778 2856 sp: SYL_BACSU Bacillus subtilis syl47.7 68.1 943 leucyl-tRNA synthetase 3341 6841 3222722 3223150 429 sp:YBAN_ECOLI Escherichia coli K12 40.4 40.4 104 hypothetical membraneprotein 3342 6842 3223445 3223089 357 sp: VAPI_BACNO Dichelobacternodosus vapI 55.8 81.4 86 virulence-associated protein 3343 6843 32246013225374 774 3344 6844 3224714 3223992 723 gp: SCC54_19 Streptomycescoelicolor 31.6 53.8 247 hypothetical protein SCC54.19 3345 6845 32255543224718 837 sp: HPCE_ECOLI Escherichia coli K12 hpcE 28.5 50.3 298bifunctional protein (homoprotocatechuate catabolism bifunctionalisomerase/decarboxylase) (2- hydroxyhepta-2,4-diene-1,7-dioate isomeraseand 5-carboxymethyl-2- oxo-hex-3-ene-1,7dioate decarboxylase) 3346 68463226687 3225563 1125 gp: AF173167_1 Pseudomonas alcaligenes xlnE 34.264.3 339 gentisate 1,2-dioxygenase or 1- hydroxy-2-naphthoatedioxygenase 3347 6847 3227689 3226910 780 sp: KDGR_ERWCH Pectobacteriumchrysanthemi 25.3 60.7 229 bacterial regulatory protein, lacl kdgRfamily or pectin degradation repressor protein 3348 6848 3227724 32290791356 sp: PCAK_PSEPU Pseudomonas putida pcaK 27.5 60.8 454 transmembranetransport protein or 4-hydroxybenzoate transporter 3349 6849 32291193230444 1326 prf: 1706191A Pseudomonas putida 28.2 49.4 476 salicylatehydroxylase 3350 6850 3232304 3231054 1251 sp: EAT2_HUMAN Homo sapienseat2 25.4 54.4 507 proton/glutamate symporter or excitatory amino acidtransporter2 3351 6851 3232596 3233105 510 pir: JC2326 Corynebacteriumglutamicum 99.4 99.4 170 tryptophan-specific permease AS019 ORF1 33526852 3233403 3234956 1554 sp: TRPE_BRELA Brevibacterium lactofermentum99.2 99.8 515 anthranilate synthase component I trpE 3353 6853 32334203233250 171 3354 6854 3234956 3235579 624 TRPG_BRELA Brevibacteriumlactofermentum 99.0 100.0 208 anthranilate synthase component II trpG3355 6855 3235602 3236645 1044 sp: TRPD_CORGL Corynebacterium glutamicum99.4 99.4 348 anthranilate ATCC 21850 trpD phosphoribosyltransferase3356 6856 3236641 3238062 1422 sp: TRPC_BRELA Brevibacteriumlactofermentum 97.3 98.3 474 indole-3-glycerol phosphate trpC synthase(IGPS) and N-(5′- phosphoribosyl) anthranilate isomerase(PRAI) 3357 68573237213 3236518 696 3358 6858 3238082 3239332 1251 sp: TRPB_BRELABrevibacterium lactofermentum 97.6 97.9 417 tryptophan synthase betachain trpB 3359 6859 3239332 3240171 840 sp: TRPA_BRELA Brevibacteriumlactofermentum 95.4 96.5 283 tryptophan synthase alpha chain trpA 33606860 3241851 3240313 1539 gp: SCJ21_17 Streptomyces coelicolor A3(2)66.6 86.8 521 hypothetical membrane protein SCJ21.17c 3361 6861 32426883241879 810 sp: PTXA_ECOLI Escherichia coli K12 ptxA 30.3 71.7 152 PTSsystem, IIA component or unknown pentitol phosphotransferase enzyme II,A component 3362 6862 3242854 3243759 906 sp: NOSF_PSEST Pseudomonasstutzeri 32.5 63.6 305 ABC transporter ATP-binding protein 3363 68633243759 3245342 1584 gp: SCH10_12 Streptomyces coelicolor A3(2) 25.257.2 547 ABC transporter SCH10.12 3364 6864 3245317 3245766 450 sp:UCRI_CHLLT Chlorobium limicola petC 32.5 63.6 305 cytchrome b6-F complexiron-sulfur subunit (Rieske iron-sulfur protein) 3365 6865 32469313245822 1110 sp: NADO_THEBR Thermoanaerobacter brockii 33.3 64.3 336NADH oxidase or NADH-dependent nadO flavin oxidoreductase 3366 68663247234 3248205 972 sp: YFEH_ECOLI Escherichia coli K12 yfeH 43.6 74.7328 hypothetical membrane protein 3367 6867 3248392 3249165 774 gp:SCI11_36 Streptomyces coelicolor A3(2) 34.0 54.6 262 hypotheticalprotein SCI11.36c 3368 6868 3249534 3249187 348 pir: A29606 Streptomycescoelicolor Plasmid 45.1 79.4 102 bacterial regulatory protein, arsR SCP1mmr family or methylenomycin A resistance protein 3369 6869 32496513250742 1092 sp: NADO_THEBR Thermoanaerobacter brockii 33.4 64.3 347NADH oxidase or NADH-dependent nadO flavin oxidoreductase 3370 68703250758 3251405 648 sp: YMY0_YEAST Saccharomyces cerevisiae 31.4 69.5226 hypothetical protein ymyO 3371 6871 3251618 3251466 153 3372 68723251934 3251743 192 3373 6873 3252300 3252133 168 3374 6874 32526363252316 321 3375 6875 3252728 3253480 753 sp: BUDC_KLETE Klebsiellaterrigena budC 26.9 52.9 238 acetoin(diacetyl) reductase (acetoindehydrogenase) 3376 6876 3253560 3253739 180 sp: YY34_MYCTUMycobacterium tuberculosis 53.5 84.5 58 hypothetical protein H37RvRv2094c 3377 6877 3255182 3253824 1359 sp: DTPT_LACLA Lactococcus lactissubsp. lactis 34.5 71.6 469 di-/tripeptide transpoter dtpT 3378 68783255549 3255719 171 3379 6879 3256298 3255744 555 sp: ACRR_ECOLIEscherichia coli K12 acrR 26.1 50.5 188 bacterial regulatory protein,tetR family 3380 6880 3257373 3256471 903 sp: CATA_ACICA Acinetobactercalcoaceticus 31.7 62.2 246 hydroxyquinol 1,2-dioxygenase catA 3381 68813258491 3257403 1089 sp: TCBF_PSESQ Pseudomonas sp. P51 43.0 75.5 351maleylacetate reductase 3382 6882 3260084 3258561 1524 sp: XYLE_ECOLIEscherichia coli K12 xylE 31.4 58.3 513 sugar transporter orD-xylose-proton symporter (D-xylose transporter) 3383 6883 32611293261989 861 sp: ICLR_SALTY Salmonella typhimurium iclR 25.7 60.7 280bacterial transcriptional regulator or acetate operon repressor 33846884 3262145 3263221 1077 sp: YDGJ_ECOLI Escherichia coli K12 ydgJ 27.255.7 357 oxidoreductase 3385 6885 3263237 3264115 879 gsp: W61761Listeria innocua strain 4450 25.9 58.2 270 diagnostic fragment proteinsequence 3386 6886 3264142 3265146 1005 sp: MI2D_BACSU SinoRhizobiummeliloti idhA 26.5 59.6 332 myo-inositol 2-dehydrogenase 3387 68873265184 3266266 1083 sp: STRI_STRGR Streptomyces griseus strI 34.1 62.4343 dehydrogenase or myo-inositol 2- dehydrogenase or streptomycinbiosynthesis protein 3388 6888 3267062 3271093 4032 pir: C70044 Bacillussubtilis yvnB 33.3 62.7 1242 phosphoesterase 3389 6889 3268557 3267913645 3390 6890 3269235 3268618 618 3391 6891 3271392 3272477 1086 33926892 3275231 3274488 744 sp: UNC1_CAEEL Caenorhabditis elegans unc1 28.657.3 206 stomatin 3393 6893 3276570 3275602 969 3394 6894 32815993276671 4929 gp: MBO18605_3 Mycobacterium bovis BCG 58.4 80.2 1660 DEADbox RNA helicase family RvD1-Rv2024c 3395 6895 3282172 3281666 507 prf:2323363AAM Mycobacterium leprae u2266k 34.8 61.0 141 hypotheticalmembrane protein 3396 6896 3282742 3283101 360 3397 6897 3282946 3282347600 sp: THID_BACSU Bacillus subtilis thiD 50.4 76.8 125phosphomethylpyrimidine kinase 3398 6898 3283141 3283383 243 pir: F70041Bacillus subtilis yvgY 46.3 70.1 67 mercuric ion-binding protein orheavy-metal-associated domain containing protein 3399 6899 32843093283473 837 prf: 2501295A Corynebacterium glutamicum 29.9 62.3 297ectoine/proline uptake protein proP 3400 6900 3285355 3284399 957 sp:FECB_ECOLI Escherichia coli K12 fecB 29.4 60.6 279 iron(III)dicitrate-binding periplasmic protein precursor or iron(III) dicitratetransport system permease protein 3401 6901 3285455 3286576 1122 sp:MRF1_SCHPO Schizosaccharomyces pombe 27.2 58.0 324 mitochondrialrespiratory function mrf1 protein or zinc-binding dehydrogenase or NADPHquinone oxidoreductase 3402 6902 3286622 3287005 384 3403 6903 32872973287079 219 3404 6904 3288190 3287393 798 sp: THID_BACSU Bacillussubtilis thiD 46.2 75.5 249 phosphomethylpyrimidine kinase 3405 69053288265 3288609 345 3406 6906 3288685 3288885 201 pir: F70041 Bacillussubtilis yvgY 41.8 70.1 67 mercuric ion-binding protein orheavy-metal-associated domain containing protein 3407 6907 32893153288971 345 sp: AZLD_BACSU Bacillus subtilis azlD 36.3 65.7 102branched-chain amino acid transport 3408 6908 3290021 3289311 711 sp:AZLC_BACSU Bacillus subtilis azlD 32.1 67.0 212 branched-chain aminoacid transport 3409 6909 3290591 3290025 567 sp: YQGE_ECOLI Escherichiacoli K12 yqgE 23.7 56.2 169 hypothetical protein 3410 6910 32919423290623 1320 sp: CCA_ECOLI Escherichia coli K12 cca 26.8 51.8 471 tRNAnucleotidyltransferase 3411 6911 3292532 3293497 966 pir: E70600Mycobacterium tuberculosis 43.6 69.2 234 mutator mutT protein H37RvRv3908 3412 6912 3292882 3292610 273 3413 6913 3293497 3296007 2511 pir:F70600 Mycobacterium tuberculosis 25.8 54.3 858 hypothetical membraneprotein H37Rv Rv3909 3414 6914 3296156 3299404 3249 pir: G70600Mycobacterium tuberculosis 35.7 60.1 1201 hypothetical membrane proteinH37Rv Rv3910 3415 6915 3297706 3298428 723 3416 6916 3299661 3300263 603sp: RPSH_PSEAE Pseudomonas aeruginosa algU 30.2 60.9 189 RNA polymerasesigma-H factor or sigma-70 factor (ECF subfamily) 3417 6917 33003713301321 951 sp: TRXB_STRCL Streptomyces clavuligerus trxB 60.4 82.5 308thioredoxin reductase 3418 6918 3301303 3300119 1185 3419 6919 33013583301729 372 sp: THI2_CHLRE Chlamydomonas reinhardtii thi2 42.0 76.5 119thioredoxin ch2, M-type 3420 6920 3301755 3302996 1242 sp: CWLB_BACSUBacillus subtilis cwlB 51.0 75.4 196 N-acetylmuramoyl-L-alanine amidase3421 6921 3302765 3301989 777 3422 6922 3303435 3304475 1041 3423 69233303616 3302999 618 pir: D70851 Mycobacterium tuberculosis 34.4 58.5 212hypothetical protein H37Rv Rv3916c 3424 6924 3304787 3303636 1152 sp:YGI2_PSEPU Pseudomonas putida ygi2 37.6 60.5 367 hypothetical protein3425 6925 3305671 3304835 837 sp: YGI1_PSEPU Mycobacterium tuberculosis65.0 78.0 272 partitioning or sporulation protein H37Rv parB 3426 69263306532 3305864 669 sp: GIDB_ECOLI Escherichia coli K12 gidB 36.0 64.7153 glucose inhibited division protein B 3427 6927 3307632 3306682 951pir: A70852 Mycobacterium tuberculosis 44.7 75.4 313 hypotheticalmembrane protein H37Rv Rv3921c 3428 6928 3308369 3307971 399 sp:RNPA_BACSU Bacillus subtilis rnpA 26.8 59.4 123 ribonuclease P proteincomponent 3429 6929 3308747 3308412 336 gp: MAU19185_1 Mycobacteriumavium rpmH 83.0 93.6 47 50S ribosomal protein L34 3430 6930 33090283309321 294 3431 6931 3309043 3308822 222 3432 6932 147980 147573 408gp: AF116184_1 Corynebacterium glutamicum 100.0 100.0 136L-aspartate-alpha-decarboxylase panD precursor 3433 6933 268001 2661541848 sp: LEU1_CORGL Corynebacterium glutamicum 100.0 100.0 6162-isopropylmalate synthase ATCC 13032 leuA 3434 6934 269068 268814 255sp: YLEU_CORGL Corynebacterium glutamicum 100.0 100.0 85 hypotheticalprotein (Brevibacterium flavum) ATCC 13032 orfX 3435 6935 270660 2716911032 sp: DHAS_CORGL Corynebacterium glutamicum 100.0 100.0 344aspartate-semialdehyde asd dehydrogenase 3436 6936 446075 446521 447 gp:AF124518_1 Corynebacterium glutamicum 100.0 100.0 149 3-dehydroquinaseASO19 aroD 3437 6937 526376 527563 1188 sp: EFTU_CORGL Corynebacteriumglutamicum 100.0 100.0 396 elongation factor Tu ATCC 13059 tuf 3438 6938569452 570771 1320 sp: SECY_CORGL Corynebacterium glutamicum 100.0 100.0440 preprotein translocase secY subuit (Brevibacterium flavum) MJ233secY 3439 6939 680044 677831 2214 sp: IDH_CORGL Corynebacteriumglutamicum 100.0 100.0 738 isocitrate dehydrogenase ATCC 13032 icd(oxalosuccinatedecarboxylase) 3440 6940 720352 718580 1773 prf: 2223173ACorynebacterium glutamicum 100.0 100.0 591 acyl-CoA carboxylase orbiotin- ATCC 13032 accBC binding protein 3441 6941 877838 879148 1311sp: CISY_CORGL Corynebacterium glutamicum 100.0 100.0 437 citratesynthase ATCC 13032 gltA 3442 6942 879276 879629 354 sp: FKBP_CORGLCorynebacterium glutamicum 100.0 100.0 118 putative binding protein orpeptidyl- ATCC 13032 fkbA prolyl cis-trans isomerase 3443 6943 944996946780 1785 sp: BETP_CORGL Corynebacterium glutamicum 100.0 100.0 595glycine betaine transporter ATCC 13032 betP 3444 6944 1030283 10290061278 sp: YLI2_CORGL Corynebacterium glutamicum 100.0 100.0 426hypothetical membrane protein ATCC 13032 orf2 3445 6945 1031871 10303691503 sp: LYSI_CORGL Corynebacterium glutamicum 100.0 100.0 501 L-lysinepermease ATCC 13032 lysI 3446 6946 1154683 1153295 1389 sp: AROP_CORGLCorynebacterium glutamicum 100.0 100.0 463 aromatic amino acid permeaseATCC 13032 aroP 3447 6947 1155676 1154729 948 pir: S52753Corynebacterium glutamicum 100.0 100.0 316 hypothetical protein ATCC13032 orf3 3448 6948 1155731 1156837 1107 prf: 2106301A Corynebacteriumglutamicum 100.0 100.0 369 succinyl diaminopimelate ATCC 13032 dapE 34496949 1219602 1218031 1572 gp: CGPUTP_1 Corynebacterium glutamicum 100.0100.0 524 proline transport system ATCC 13032 putP 3450 6950 12382741239923 1650 sp: SYR_CORGL Corynebacterium glutamicum 100.0 100.0 550arginyl-tRNA synthetase AS019 ATCC 13059 argS 3451 6951 1239929 12412631335 sp: DCDA_CORGL Corynebacterium glutamicum 100.0 100.0 445diaminopimelate (DAP) AS019 ATCC 13059 lysA decarboxylase (meso-diaminopimelate decarboxylase) 3452 6952 1242507 1243841 1335 sp:DHOM_CORGL Corynebacterium glutamicum 100.0 100.0 445 homoserinedehydrogenase AS019 ATCC 13059 hom 3453 6953 1243855 1244781 927 sp:KHSE_CORGL Corynebacterium glutamicum 100.0 100.0 309 homoserine kinaseAS019 ATCC 13059 thrB 3454 6954 1327617 1328243 627 gsp: W37716Corynebacterium glutamicum 100.0 100.0 216 ion channel subunit R127 orf33455 6955 1328953 1328246 708 sp: LYSE_CORGL Corynebacterium glutamicum100.0 100.0 236 lysine exporter protein R127 lysE 3456 6956 13290151329884 870 sp: LYSG_CORGL Corynebacterium glutamicum 100.0 100.0 290lysine export regulator protein R127 lysG 3457 6957 1338131 1340008 1878sp: ILVB_CORGL Corynebacterium glutamicum 100.0 100.0 626 acetohydroxyacid synthase, large ATCC 13032 ilvB subunit 3458 6958 1340025 1340540516 pir: B48648 Corynebacterium glutamicum 100.0 100.0 172 acetohydroxyacid synthase, small ATCC 13032 ilvN subunit 3459 6959 1340724 13417371014 pir: C48648 Corynebacterium glutamicum 100.0 100.0 338 acetohydroxyacid isomeroreductase ATCC 13032 ilvC 3460 6960 1353489 1354508 1020 sp:LEU3_CORGL Corynebacterium glutamicum 100.0 100.0 340 3-isopropylmalatedehydrogenase ATCC 13032 leuB 3461 6961 1423217 1425265 2049 prf:2014259A Corynebacterium glutamicum 100.0 100.0 683 PTS system,phosphoenolpyruvate KCTC1445 ptsM sugar phosphotransferase (mannose andglucose transport) 3462 6962 1466491 1467372 882 sp: ARGB_CORGLCorynebacterium glutamicum 100.0 100.0 294 acetylglutamate kinase ATCC13032 argB 3463 6963 1468565 1469521 957 sp: OTCA_CORGL Corynebacteriumglutamicum 100.0 100.0 319 ornithine carbamoyltransferase ATCC 13032argF 3464 6964 1469528 1470040 513 gp: AF041436_1 Corynebacteriumglutamicum 100.0 100.0 171 arginine repressor ASO19 argR 3465 69651544554 1543154 1401 gp: CGL238250_1 Corynebacterium glutamicum 100.0100.0 467 NADH dehydrogenase ATCC 13032 ndh 3466 6966 1586725 1586465261 gp: AF086704_1 Corynebacterium glutamicum 100.0 100.0 87phosphoribosyl-ATP- ASO19 hisE pyrophosphohydrolase 3467 6967 16752081674123 1086 gp: CGL007732_4 Corynebacterium glutamicum 100.0 100.0 362ornithine-cyclodecarboxylase ATCC 13032 ocd 3468 6968 1676623 16752681356 gp: CGL007732_3 Corynebacterium glutamicum 100.0 100.0 452 ammoniumuptake protein, high ATCC 13032 amt affinity 3469 6969 1677279 1677049231 gp: CGL007732_2 Corynebacterium glutamicum 100.0 100.0 77protein-export membrane protein ATCC 13032 secG secG 3470 6970 16801431677387 2757 prf: 1509267A Corynebacterium glutamicum 100.0 100.0 919phosphoenolpyruvate carboxylase ATCC 13032 ppc 3471 6971 1720898 17196691230 gp: AF124600_1 Corynebacterium glutamicum 100.0 100.0 410chorismate synthase (5- AS019 aroC enolpyruvylshikimate-3-phosphatephospholyase) 3472 6972 1880490 1882385 1896 pir: B55225 Corynebacteriumglutamicum 100.0 100.0 632 restriction endonuclease ATCC 13032 cglIIR3473 6973 2020854 2021846 993 prf: 2204286D Corynebacterium glutamicum100.0 100.0 331 sigma factor or RNA polymerase ATCC 13869 sigBtranscription factor 3474 6974 2060620 2061504 885 sp: GLUB_CORGLCorynebacterium glutamicum 100.0 100.0 295 glutamate-binding proteinATCC 13032 gluB 3475 6975 2065116 2063989 1128 sp: RECA_CORGLCorynebacterium glutamicum 100.0 100.0 376 recA protein AS019 recA 34766976 2080183 2079281 903 sp: DAPA_BRELA Corynebacterium glutamicum 100.0100.0 301 dihydrodipicolinate synthase (Brevibacterium lactofermentum)ATCC 13869 dapA 3477 6977 2081934 2081191 744 sp: DAPB_CORGLCorynebacterium glutamicum 100.0 100.0 248 dihydrodipicolinate reductase(Brevibacterium lactofermentum) ATCC 13869 dapB 3478 6978 21153632113864 1500 gp: CGA224946_1 Corynebacterium glutamicum 100.0 100.0 500L-malate dehydrogenase (acceptor) R127 mqo 3479 6979 2171741 21696662076 gp: CAJ10319_4 Corynebacterium glutamicum 100.0 100.0 692uridilylyltransferase, uridilylyl- ATCC 13032 glnD removing enzyme 34806980 2172086 2171751 336 gp: CAJ10319_3 Corynebacterium glutamicum 100.0100.0 112 nitrogen regulatory protein P-II ATCC 13032 glnB 3481 69812173467 2172154 1314 gp: CAJ10319_2 Corynebacterium glutamicum 100.0100.0 438 ammonium transporter ATCC 13032 amtP 3482 6982 2196082 21947421341 pir: S32227 Corynebacterium glutamicum 100.0 100.0 447 glutamatedehydrogenase (NADP+) ATCC 17965 gdhA 3483 6983 2207092 2205668 1425 sp:KPYK_CORGL Corynebacterium glutamicum 100.0 100.0 475 pyruvate kinaseAS019 pyk 3484 6984 2317550 2316582 969 gp: AF096280_1 Corynebacteriumglutamicum 100.0 100.0 323 glucokinase ATCC 13032 glk 3485 6985 23488292350259 1431 prf: 2322244A Corynebacterium glutamicum 100.0 100.0 477glutamine synthetase ATCC 13032 glnA 3486 6986 2355042 2353600 1443 sp:THRC_CORGL Corynebacterium glutamicum 100.0 100.0 481 threonine synthasethrC 3487 6987 2450172 2448328 1845 prf: 2501295B Corynebacteriumglutamicum 100.0 100.0 615 ectoine/proline/glycine betaine ATCC 13032ectP carrier 3488 6988 2470141 2467925 2217 pir: I40715 Corynebacteriumglutamicum 100.0 100.0 739 malate synthase ATCC 13032 aceB 3489 69892470740 2472035 1296 pir: I40713 Corynebacterium glutamicum 100.0 100.0432 isocitrate lyase ATCC 13032 aceA 3490 6990 2497776 2496670 1107 sp:PROB_CORGL Corynebacterium glutamicum 100.0 100.0 369 glutamate 5-kinaseATCC 17965 proB 3491 6991 2591469 2590312 1158 gp: AF126953_1Corynebacterium glutamicum 100.0 100.0 386 cystathionine gamma-synthaseASO19 metB 3492 6992 2680127 2679684 444 gp: AF112535_2 Corynebacteriumglutamicum 100.0 100.0 148 ribonucleotide reductase ATCC 13032 nrdI 34936993 2680649 2680419 231 gp: AF112535_1 Corynebacterium glutamicum 100.0100.0 77 glutaredoxin ATCC 13032 nrdH 3494 6994 2787715 2786756 960 sp:DDH_CORGL Corynebacterium glutamicum 100.0 100.0 320meso-diaminopimelate D- KY10755 ddh dehydrogenase 3495 6995 28880782887944 135 gp: CGL238703_1 Corynebacterium glutamicum 100.0 100.0 45porin or cell wall channel forming MH20-22B porA protein 3496 69962936505 2935315 1191 sp: ACKA_CORGL Corynebacterium glutamicum 100.0100.0 397 acetate kinase ATCC 13032 ackA 3497 6997 2937494 2936508 987prf: 2516394A Corynebacterium glutamicum 100.0 100.0 329 phosphateacetyltransferase ATCC 13032 pta 3498 6998 2961342 2962718 1377 prf:2309322A Corynebacterium glutamicum 100.0 100.0 459 multidrug resistanceprotein or ATCC 13032 cmr macrolide-efflux pump or drug: protonantiporter 3499 6999 2966161 2963606 2556 sp: CLPB_CORGL Corynebacteriumglutamicum 100.0 100.0 852 ATP-dependent protease regulatory ATCC 13032clpB subunit 3500 7000 3099522 3098578 945 prf: 1210266A Corynebacteriumglutamicum 100.0 100.0 315 prephenate dehydratase pheA 3501 7001 32740743272563 1512 prf: 2501295A Corynebacterium glutamicum 100.0 100.0 504ectoine/proline uptake protein ATCC 13032 proP

EXAMPLE 2

Determination of Effective Mutation Site

(1) Identification of Mutation Site Based on the Comparison of the GeneNucleotide Sequence of Lysine-Producing B-6 Strain with that of WildType Strain ATCC 13032

Corynebacterium glutamicum B-6, which is resistant toS-(2-aminoethyl)cysteine (AEC), rifampicin, streptomycin and6-azauracil, is a lysine-producing mutant having been mutated and bredby subjecting the wild type ATCC 13032 strain to multiple rounds ofrandom mutagenesis with a mutagen, N-methyl-N′-nitro-N-nitrosoguanidine(NTG) and screening (Appl. Microbiol. Biotechnol., 32: 269-273 (1989)).First, the nucleotide sequences of genes derived from the B-6 strain andconsidered to relate to the lysine production were determined by amethod similar to the above. The genes relating to the lysine productioninclude lysE and lysG which are lysine-excreting genes; ddh, dapA, homand lysC (encoding diaminopimelate dehydrogenase, dihydropicolinatesynthase, homoserine dehydrogenase and aspartokinase, respectively)which are lysine-biosynthetic genes; and pyc and zwf (encoding pyruvatecarboxylase and glucose-6-phosphate dehydrogenase, respectively) whichare glucose-metabolizing genes. The nucleotide sequences of the genesderived from the production strain were compared with the correspondingnucleotide sequences of the ATCC 13032 strain genome represented by SEQID NOS:1 to 3501 and analyzed. As a result, mutation points wereobserved in many genes. For example, no mutation site was observed inlysE, lysG, ddh, dapA, and the like, whereas amino acid replacementmutations were found in hom, lysC, pyc, zwf, and the like. Among thesemutation points, those which are considered to contribute to theproduction were extracted on the basis of known biochemical or geneticinformation. Among the mutation points thus extracted, a mutation,Val59Ala, in hom and a mutation, Pro458Ser, in pyc were evaluatedwhether or not the mutations were effective according to the followingmethod.

(2) Evaluation of Mutation, Val59Ala, in hom and Mutation, Pro458Ser, inpyc

It is known that a mutation in horn inducing requirement or partialrequirement for homoserine imparts lysine productivity to a wild typestrain (Amino Acid Fermentation, ed. by Hiroshi Aida et al., JapanScientific Societies Press). However, the relationship between themutation, Val59Ala, in hom and lysine production is not known. It can beexamined whether or not the mutation, Val59Ala, in hom is an effectivemutation by introducing the mutation to the wild type strain andexamining the lysine productivity of the resulting strain. On the otherhand, it can be examined whether or not the mutation, Pro458Ser, in pycis effective by introducing this mutation into a lysine-producing strainwhich has a deregulated lysine-bioxynthetic pathway and is free from thepyc mutation, and comparing the lysine productivity of the resultingstrain with the parent strain. As such a lysine-producing bacterium, No.58 strain (FERM BP-7134) was selected (hereinafter referred to the“lysine-producing No. 58 strain” or the “No. 58 strain”). Based on theabove, it was determined that the mutation, Val59Ala, in hom and themutation, Pro458Ser, in pyc were introduced into the wild type strain ofCorynebacterium glutamicum ATCC 13032 (hereinafter referred to as the“wild type ATCC 13032 strain” or the “ATCC 13032 strain”) and thelysine-producing No. 58 strain, respectively, using the gene replacementmethod. A plasmid vector pCES30 for the gene replacement for theintroduction was constructed by the following method.

A plasmid vector pCE53 having a kanamycin-resistant gene and beingcapable of autonomously replicating in Coryneform bacteria (Mol. Gen.Genet., 196: 175-178 (1984)) and a plasmid pMOB3 (ATCC 77282) containinga levansucrase gene (sacB) of Bacillus subtilis (Molecular Microbiology,6: 1195-1204 (1992)) were each digested with PstI. Then, after agarosegel electrophoresis, a pCE53 fragment and a 2.6 kb DNA fragmentcontaining sacB were each extracted and purified using GENECLEAN Kit(manufactured by BIO 101). The pCE53 fragment and the 2.6 kb DNAfragment were ligated using Ligation Kit ver. 2 (manufactured by TakaraShuzo), introduced into the ATCC 13032 strain by the electroporationmethod (FEMS Microbiology Letters, 65: 299 (1989)), and cultured on BYGagar medium (medium prepared by adding 10 g of glucose, 20 g of peptone(manufactured by Kyokuto Pharmaceutical), 5 g of yeast extract(manufactured by Difco), and 16 g of Bactoagar (manufactured by Difco)to 1 liter of water, and adjusting its pH to 7.2) containing 25 μg/mlkanamycin at 30° C. for 2 days to obtain a transformant acquiringkanamycin-resistance. As a result of digestion analysis with restrictionenzymes, it was confirmed that a plasmid extracted from the resultingtransformant by the alkali SDS method had a structure in which the 2.6kb DNA fragment had been inserted into the PstI site of pCE53. Thisplasmid was named pCES30.

Next, two genes having a mutation point, hom and pyc, were amplified byPCR, and inserted into pCES30 according to the TA cloning method (BioExperiment Illustrated vol. 3, published by Shujunsha). Specifically,pCES30 was digested with BamHI (manufactured by Takara Shuzo), subjectedto an agarose gel electrophoresis, and extracted and purified usingGENECLEAN Kit (manufactured by BIO 101). The both ends of the resultingpCES30 fragment were blunted with DNA Blunting Kit (manufactured byTakara Shuzo) according to the attached protocol. The blunt-ended pCES30fragment was concentrated by extraction with phenol/chloroform andprecipitation with ethanol, and allowed to react in the presence of Taqpolymerase (manufactured by Roche Diagnostics) and dTTP at 70° C. for 2hours so that a nucleotide, thymine (T), was added to the 3′-end toprepare a T vector of pCES30.

Separately, chromosomal DNA was prepared from the lysine-producing B-6strain according to the method of Saito et al. (Biochem. Biophys. Acta,72: 619 (1963)). Using the chromosomal DNA as a template, PCR wascarried out with Pfu turbo DNA polymelase (manufactured by Stratagene).In the mutated hom gene, the DNAs having the nucleotide sequencesrepresented by SEQ ID NOS:7002 and 7003 were used as the primer set. Inthe mutated pyc gene, the DNAs having the nucleotide sequencesrepresented by SEQ ID NOS:7004 and 7005 were used as the primer set. Theresulting PCR product was subjected to agarose gel electrophoresis, andextracted and purified using GENEGLEAN Kit (manufactured by BIO 101).Then, the PCR product was allowed to react in the presence of Taqpolymerase (manufactured by Roche Diagnostics) and dATP at 72° C. for 10minutes so that a nucleotide, adenine (A), was added to the 3′-end.

The above pCES30 T vector fragment and the mutated hom gene (1.7 kb) ormutated pyc gene (3.6 kb) to which the nucleotide A had been added ofthe PCR product were concentrated by extraction with phenol/chloroformand precipitation with ethanol, and then ligated using Ligation Kit ver.2. The ligation products were introduced into the ATCC 13032 strainaccording to the electroporation method, and cultured on BYG agar mediumcontaining 25 μg/ml kanamycin at 30° C. for 2 days to obtainkanamycin-resistant transformants. Each of the resulting transformantswas cultured overnight in BYG liquid medium containing 25 μg/mlkanamycin, and a plasmid was extracted from the culturing solutionmedium according to the alkali SDS method. As a result of digestionanalysis using restriction enzymes, it was confirmed that the plasmidhad a structure in which the 1.7 kb or 3.6 kb DNA fragment had beeninserted into pCES30. The plasmids thus constructed were namedrespectively pChom59 and pCpyc458.

The introduction of the mutations to the wild type ATCC 13032 strain andthe lysine-producing No. 58 strain according to the gene replacementmethod was carried out according to the following method. Specifically,pChom59 and pCpyc458 were introduced to the ATCC 13032 strain and theNo. 58 strain, respectively, and strains in which the plasmid isintegrated into the chromosomal DNA by homologous recombination wereselected using the method of Ikeda et al. (Microbiology 144: 1863(1998)). Then, the stains in which the second homologous recombinationwas carried out were selected by a selection method, making use of thefact that the Bacillus subtilis levansucrase encoded by pCES30 produceda suicidal substance (J. of Bacteriol., 174: 5462 (1992)). Among theselected strains, strains in which the wild type hom and pyc genespossessed by the ATCC 13032 strain and the No. 58 strain were replacedwith the mutated hom and pyc genes, respectively, were isolated. Themethod is specifically explained below.

One strain was selected from the transformants containing the plasmid,pChom59 or pCpyc458, and the selected strain was cultured in BYG mediumcontaining 20 μg/ml kanamycin, and pCG11 (Japanese Published ExaminedPatent Application No. 91827/94) was introduced thereinto by theelectroporation method. pCG11 is a plasmid vector having aspectinomycin-resistant gene and a replication origin which is the sameas pCE53. After introduction of the pCG11, the strain was cultured onBYG agar medium containing 20 μg/ml kanamycin and 100 μg/mlspectinomycin at 30° C. for 2 days to obtain both the kanamycin- andspectinomycin-resistant transformant. The chromosome of one strain ofthese transformants was examined by the Southern blotting hybridizationaccording to the method reported by Ikeda et al. (Microbiology, 144:1863 (1998)). As a result, it was confirmed that pChom59 or pCpyc458 hadbeen integrated into the chromosome by the homologous recombination ofthe Cambell type. In such a strain, the wild type and mutated hom or pycgenes are present closely on the chromosome, and the second homologousrecombination is liable to arise therebetween.

Each of these transformants (having been recombined once) was spread onSuc agar medium (medium prepared by adding 100 g of sucrose, 7 g of meatextract, 10 g of peptone, 3 g of sodium chloride, 5 g of yeast extract(manufactured by Difco), and 18 g of Bactoagar (manufactured by Difco)to 1 liter of water, and adjusting its pH 7.2) and cultured at 30° C.for a day. Then the colonies thus growing were selected in each case.Since a strain in which the sacb gene is present converts sucrose into asuicide substrate, it cannot grow in this medium (J. Bacteriol., 174:5462 (1992)). On the other hand, a strain in which the sacB gene wasdeleted due to the second homologous recombination between the wild typeand the mutated hom or pyc genes positioned closely to each other formsno suicide substrate and, therefore, can grow in this medium. In thehomologous recombination, either the wild type gene or the mutated geneis deleted together with the sacB gene. When the wild type is deletedtogether with the sacb gene, the gene replacement into the mutated typearises.

Chromosomal DNA of each the thus obtained second recombinants wasprepared by the above method of Saito et al. PCR was carried out usingPfu turbo DNA polymerase (manufactured by Stratagene) and the attachedbuffer. In the hom gene, DNAs having the nucleotide sequencesrepresented by SEQ ID NOS:7002 and 7003 were used as the primer set.Also, in the pyc gene was used, DNAs having the nucleotide sequencesrepresented by SEQ ID NOS:7004 and 7005 were used as the primer set. Thenucleotide sequences of the PCR products were determined by theconventional method so that it was judged whether the hom or pyc gene ofthe second recombinant was a wild type or a mutant. As a result, thesecond recombinant which were called HD-1 and No. 58pyc were targetstrains having the mutated hom gene and pyc gene, respectively.

(3) Lysine Production Test of HD-1 and No. 58pyc Strains

The HD-1 strain (strain obtained by incorporating the mutation,Val59Ala, in the hom gene into the ATCC 13032 strain) and the No. 58pycstrain (strain obtained by incorporating the mutation, Pro458Ser, in thepyc gene into the lysine-producing No. 58 strain) were subjected to aculture test in a 5 l jar fermenter by using the ATCC 13032 strain andthe lysine-producing No. 58 strain respectively as a control. Thuslysine production was examined.

After culturing on BYG agar medium at 30° C. for 24 hours, each strainwas inoculated into 250 ml of a seed medium (medium prepared by adding50 g of sucrose, 40 g of corn steep liquor, 8.3 g of ammonium sulfate, 1g of urea, 2 g of potassium dihydrogenphosphate, 0.83 g of magnesiumsulfate heptahydrate, 10 mg of iron sulfate heptahydrate, 1 mg of coppersulfate pentahydrate, 10 mg of zinc sulfate hentahydrate, 10 mg ofβ-alanine, 5 mg of nicotinic acid, 1.5 mg of thiamin hydrochloride, and0.5 mg of biotin to 1 liter of water, and adjusting its pH to 7.2, thento which 30 g of calcium carbonate had been added) contained in a 2 lbuffle-attached Erlenmeyer flask and cultured therein at 30° C. for 12to 16 hours. A total amount of the seed culturing medium was inoculatedinto 1,400 ml of a main culture medium (medium prepared by adding 60 gof glucose, 20 g of corn steep liquor, 25 g of ammonium chloride, 2.5 gof potassium dihydrogenphosphate, 0.75 g of magnesium sulfateheptahydrate, 50 mg of iron sulfate heptahydrate, 13 mg of manganesesulfate pentahydrate, 50 mg of calcium chloride, 6.3 mg of coppersulfate pentahydrate, 1.3 mg of zinc sulfate heptahydrate, 5 mg ofnickel chloride hexahydrate, 1.3 mg of cobalt chloride hexahydrate, 1.3mg of ammonium molybdenate tetrahydrate, 14 mg of nicotinic acid, 23 mgof β-alanine, 7 mg of thiamin hydrochloride, and 0.42 mg of biotin to 1liter of water) contained in a 5 l jar fermenter and cultured therein at32° C., 1 vvm and 800 rpm while controlling the pH to 7.0 with aqueousammonia. When glucose in the medium had been consumed, a glucose feedingsolution (medium prepared by adding 400 g glucose and 45 g of ammoniumchloride to 1 liter of water) was continuously added. The addition offeeding solution was carried out at a controlled speed so as to maintainthe dissolved oxygen concentration within a range of 0.5 to 3 ppm Afterculturing for 29 hours, the culture was terminated. The cells wereseparated from the culture medium by centrifugation and then L-lysinehydrochloride in the supernatant was quantified by high performanceliquid chromatography (HPLC). The results are shown in Table 2 below.

TABLE 2 Strain L-Lysine hydrochloride yield (g/l) ATCC 13032 0 HD-1 8No. 58 45 No. 58pyc 51

As is apparent from the results shown in Table 2, the lysineproductivity was improved by introducing the mutation, Val59Ala, in thehom gene or the mutation, Pro458Ser, in the pyc gene. Accordingly, itwas found that the mutations are both effective mutations relating tothe production of lysine. Strain, AHP-3, in which the mutation,Val59Ala, in the hom gene and the mutation, Pro458Ser, in the pyc genehave been introduced into the wild type ATCC 13032 strain together withthe mutation, Thr331Ile in the lysC gene has been deposited on Dec. 5,2000, in National Institute of Bioscience and Human Technology, Agencyof Industrial Science and Technology (Higashi 1-1-3, Tsukuba-shi,Ibaraki, Japan) as FERM BP-7382.

EXAMPLE 3

Reconstruction of Lysine-Producing Strain Based on Genome Information

The lysine-producing mutant B-6 strain (Appl. Microbiol. Biotechnol.,32: 269-273 (1989)), which has been constructed by multiple round randommutagenesis with NTG and screening from the wild type ATCC 13032 strain,produces-a remarkably large amount of lysine hydrochloride when culturedin a jar at 32° C. using glucose as a carbon source. However, since thefermentation period is long, the production rate is less than 2.1 g/l/h.Breeding to reconstitute only effective mutations relating to theproduction of lysine among the estimated at least 300 mutationsintroduced into the B-6 strain in the wild type ATCC 13032 strain wasperformed.

(1) Identification of Mutation Point and Effective Mutation by Comparingthe Gene Nucleotide Sequence of the B-6 Strain with that of the ATCC13032 Strain

As described above, the nucleotide sequences of genes derived from theB-6 strain were compared with the corresponding nucleotide sequences ofthe ATCC 13032 strain genome represented by SEQ ID NOS:1 to 3501 andanalyzed to identify many mutation points accumulated in the chromosomeof the B-6 strain. Among these, a mutation, Val591Ala, in hom, amutation, Thr311Ile, in lysC, a mutation, Pro458Ser, in pyc and amutation, Ala213Thr, in zwf were specified as effective mutationsrelating to the production of lysine. Breeding to reconstitute the 4mutations in the wild type strain and for constructing of anindustrially important lysine-producing strain was carried out accordingto the method shown below.

(2) Construction of Plasmid for Gene Replacement Having Mutated Gene

The plasmid for gene replacement, pChom59, having the mutated hom geneand the plasmid for gene replacement, pCpyc458, having the mutated pycgene were prepared in the above Example 2(2). Plasmids for genereplacement having the mutated lysC and zwf were produced as describedbelow.

The lysC and zwf having mutation points were amplified by PCR, andinserted into a plasmid for gene replacement, pCES30, according to theTA cloning method described in Example 2(2) (Bio Experiment Illustrated,Vol. 3).

Separately, chromosomal DNA was prepared from the lysine-producing B-6strain according to the above method of Saito et al. Using thechromosomal DNA as a template, PCR was carried out with Pfu turbo DNApolymerase (manufactured by Stratagene). In the mutated lysC gene, theDNAs having the nucleotide sequences represented by SEQ ID NOS:7006 and7007 were used as the primer set. In the mutated zwf gene, the DNAshaving the nucleotide sequences represented by SEQ ID NOS:7008 and 7009as the primer set. The resulting PCR product was subjected to agarosegel electrophoresis, and extracted and purified using GENEGLEAN Kit(manufactured by BIO 101). Then, the PCR product was allowed to react inthe presence of Taq DNA polymerase (manufactured by Roche Diagnostics)and dATP at 72° C. for 10 minutes so that a nucleotide, adenine (A), wasadded to the 3′-end.

The above pCES30 T vector fragment and the mutated lysC gene (1.5 kb) ormutated zwf gene (2.3 kb) to which the nucleotide A had been added ofthe PCR product were concentrated by extraction with phenol/chloroformand precipitation with ethanol, and then ligated using Ligation Kit ver.2. The ligation products were introduced into the ATCC 13032 strainaccording to the electroporation method, and cultured on BYG agar mediumcontaining 25 μg/ml kanamycin at 30° C. for 2 days to obtainkanamycin-resistant transformants. Each of the resulting transformantswas cultured overnight in BYG liquid medium containing 25 μg/mlkanamycin, and a plasmid was extracted from the culturing solutionmedium according to the alkali SDS method. As a result of digestionanalysis using restriction enzymes, it was confirmed that the plasmidhad a structure in which the 1.5 kb or 2.3 kb DNA fragment had beeninserted into pCES30. The plasmids thus constructed were namedrespectively pClysC311 and pCzwf213.

(3) Introduction of Mutation, Thr311Ile, in lysC into One Point MutantHD-1

Since the one mutation point mutant HD-1 in which the mutation,Val59Ala, in hom was introduced into the wild type ATCC 13032 strain hadbeen obtained in Example 2(2), the mutation, Thr311Ile, in lysC wasintroduced into the HD-1 strain using pClysC311 produced in the above(2) according to the gene replacement method described in Example 2(2).PCR was carried out using chromosomal DNA of the resulting strain and,as the primer set, DNAs having the nucleotide sequences represented bySEQ ID NOS:7006 and 7007 in the same manner as in Example 2(2). As aresult of the fact that the nucleotide sequence of the PCR product wasdetermined in the usual manner, it was confirmed that the strain whichwas named AHD-2 was a two point mutant having the mutated lysC gene inaddition to the mutated hom gene.

(4) Introduction of Mutation, Pro458Ser, in pyc into Two Point MutantAHD-2

The mutation, Pro458Ser, in pyc was introduced into the AHD-2 strainusing the pCpyc458 produced in Example 2(2) by the gene replacementmethod described in Example 2(2). PCR was carried out using chromosomalDNA of the resulting strain and, as the primer set, DNAs having thenucleotide sequences represented by SEQ ID NOS:7004 and 7005 in the samemanner as in Example 2(2). As a result of the fact that the nucleotidesequence of the PCR product was determined in the usual manner, it wasconfirmed that the strain which was named AHD-3 was a three point mutanthaving the mutated pyc gene in addition to the mutated hom gene and lysCgene.

(5) Introduction of Mutation, Ala213Thr, in zwf into Three Point MutantAHP-3

The mutation, Ala213Thr, in zwf was introduced into the AHP-3 strainusing the pCzwf458 produced in the above (2) by the gene replacementmethod described in Example 2(2). PCR was carried out using chromosomalDNA of the resulting strain and, as the primer set, DNAs having thenucleotide sequences represented by SEQ ID NOS:7008 and 7009 in the samemanner as in Example 2(2). As a result of the fact that the nucleotidesequence of the PCR product was determined in the usual manner, it wasconfirmed that the strain which was named APZ-4 was a four point mutanthaving the mutated zwf gene in addition to the mutated hom gene, lysCgene and pyc gene.

(6) Lysine Production Test on HD-1, AHD-2, AHP-3 and APZ-4 Strains

The HD-1, AHD-2, AHP-3 and APZ-4 strains obtained above were subjectedto a culture test in a 5 l jar fermenter in accordance with the methodof Example 2(3).

Table 3 shows the results.

TABLE 3 L-Lysine hydrochloride Productivity Strain (g/l) (g/l/h) HD-1 80.3 AHD-2 73 2.5 AHP-3 80 2.8 APZ-4 86 3.0

Since the lysine-producing mutant B-6 strain which has been bred basedon the random mutation and selection shows a productivity of less than2.1 g/l/h, the APZ-4 strain showing a high productivity of 3.0 g/l/h isuseful in industry.

(7) Lysine Fermentation by APZ-4 Strain at High Temperature

The APZ-4 strain, which had been reconstructed by introducing 4effective mutations into the wild type strain, was subjected to theculturing test in a 5 l jar fermenter in the same manner as in Example2(3), except that the culturing temperature was changed to 40° C.

The results are shown in Table 4.

TABLE 4 Temperature L-Lysine hydrochloride Productivity (° C.) (g/l)(g/l/h) 32 86 3.0 40 95 3.3

As is apparent from the results shown in Table 4, the lysinehydrochloride titer and productivity in culturing at a high temperatureof 40° C. comparable to those at 32° C. were obtained. In the mutatedand bred lysine-producing B-6 strain constructed by repeating randommutation and selection, the growth and the lysine productivity arelowered at temperatures exceeding 34° C. so that lysine fermentationcannot be carried out, whereas lysine fermentation can be carried outusing the APZ-4 strain at a high temperature of 40° C. so that the loadof cooling is greatly reduced and it is industrially useful. The lysinefermentation at high temperatures can be achieved by reflecting the hightemperature adaptability inherently possessed by the wild type strain onthe APZ-4 strain.

As demonstrated in the reconstruction of the lysine-producing strain,the present invention provides a novel breeding method effective foreliminating the problems in the conventional mutants and acquiringindustrially advantageous strains. This methodology which reconstitutesthe production strain by reconstituting the effective mutation is anapproach which is efficiently carried out using the nucleotide sequenceinformation of the genome disclosed in the present invention, and itseffectiveness was found for the first time in the present invention.

EXAMPLE 4

Production of DNA Microarray and use thereof

A DNA microarray was produced based on the nucleotide sequenceinformation of the ORF deduced from the full nucleotide sequences ofCorynebacterium glutamicum ATCC 13032 using software, and genes of whichexpression is fluctuated depending on the carbon source during culturingwere searched.

(1) Production of DNA Microarray

Chromosomal DNA was prepared from Corynebacterium glutamicum ATCC 13032by the method of Saito et al. (Biochem. Biophys. Acta, 72: 619 (1963)).Based on 24 genes having the nucleotide sequences represented by SEQ IDNOS:207, 3433, 281, 3435, 3439, 765, 3445, 1226, 1229, 3448, 3451, 3453,3455, 1743, 3470, 2132, 3476, 3477, 3485, 3488, 3489, 3494, 3496, and3497 from the ORFs shown in Table 1 deduced from the full genomenucleotide sequence of Corynebacterium glutamicum ATCC 13032 usingsoftware and the nucleotide sequence of rabbit globin gene (GenBankAccession No. V00882) used as an internal standard, oligo DNA primersfor PCR amplification represented by SEQ ID NOS:7010 to 7059 targetingthe nucleotide sequences of the genes were synthesized in a usualmanner.

As the oligo DNA primers used for the PCR,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7010 and7011 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:207,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7012 and7013 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3433,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7014 and7015 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:281,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7016 and7017 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3435,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7018 and7019 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3439,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7020 and7021 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:765,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7022 and7023 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3445,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7024 and7025 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:1226,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7026 and7027 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:1229,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7028 and7029 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3448,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7030 and7031 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3451,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7032 and7033 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3453,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7034 and7035 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3455,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7036 and7037 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:1743,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7038 and7039 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3470,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7040 and7041 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:2132,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7042 and7043 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3476,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7044 and7045 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3477,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7046 and7047 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3485,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7048 and7049 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3488,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7050 and7051 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3489,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7052 and7053 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3494,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7054 and7055 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3496,

DNAs having the nucleotide sequence represented by SEQ ID NOS:7056 and7057 were used for the amplification of the DNA having the nucleotidesequence represented by SEQ ID NO:3497, and

DNAs having the nucleotide sequence represented by SEQ ID NOS:7058 and7059 were used for the amplification of the DNA having the nucleotidesequence of the rabbit globin gene,

-   -   as the respective primer set.

The PCR was carried for 30 cycles with each cycle consisting of 15seconds at 95° C. and 3 minutes at 68° C. using a thermal cycler(GeneAmp PCR system 9600, manufactured by Perkin Elmer), TaKaRa EX-Taq(manufactured by Takara Shuzo), 100 ng of the chromosomal DNA and thebuffer attached to the TaKaRa Ex-Taq reagent. In the case of the rabbitglobin gene, a single-stranded cDNA which had been synthesized fromrabbit globin mRNA (manufactured by Life Technologies) according to themanufacture's instructions using a reverse transcriptase RAV-2(manufactured by Takara Shuzo). The PCR product of each gene thusamplified was subjected to agarose gel electrophoresis and extracted andpurified using QIAquick Gel Extraction Kit (manufactured by QIAGEN). Thepurified PCR product was concentrated by precipitating it with ethanoland adjusted to a concentration of 200 ng/μl. Each PCR product wasspotted on a slide glass plate (manufactured by Matsunami Glass) havingMAS coating in 2 runs using GTMASS SYSTEM (manufactured by Nippon Laser& Electronics Lab.) according to the manufacture's instructions.

(2) Synthesis of Fluorescence Labeled cDNA

The ATCC 13032 strain was spread on BY agar medium (medium prepared byadding 20 g of peptone (manufactured by Kyokuto Pharmaceutical), 5 g ofyeast extract (manufactured by Difco), and 16 g of Bactoagar(manufactured by Difco) to in 1 liter of water and adjusting its pH to7.2) and cultured at 30° C. for 2 days. Then, the cultured strain wasfurther inoculated into 5 ml of BY liquid medium and cultured at 30° C.overnight. Then, the cultured strain was further inoculated into 30 mlof a minimum medium (medium prepared by adding 5 g of ammonium sulfate,5 g of urea, 0.5 g of monopotassium dihydrogenphosphate, 0.5 g ofdipotassium monohydrogenphosphate, 20.9 g of morpholinopropanesulfonicacid, 0.25 g of magnesium sulfate heptahydrate, 10 mg of calciumchloride dihydrate, 10 mg of manganese sulfate monohydrate, 10 mg offerrous sulfate heptahydrate, 1 mg of zinc sulfate heptahydrate, 0.2 mgcopper sulfate, and 0.2 mg biotin to 1 liter of water, and adjusting itspH to 6.5) containing 110 mmol/l glucose or 200 mmol/l ammonium acetate,and cultured in an Erlenmyer flask at 30° to give 1.0 of absorbance at660 nm. After the cells were prepared by centrifuging at 4° C. and 5,000rpm for 10 minutes, total RNA was prepared from the resulting cellsaccording to the method of Bormann et al. (Molecular Microbiology, 6:317-326 (1992)). To avoid contamination with DNA, the RNA was treatedwith DnaseI (manufactured by Takara Shuzo) at 37° C. for 30 minutes andthen further purified using Qiagen RNeasy MiniKit (manufactured byQIAGEN) according to the manufacture's instructions. To 30 μg of theresulting total RNA, 0.6 μl of rabbit globin mRNA (50 ng/μl,manufactured by Life Technologies) and 1 μl of a random 6 mer primer(500 ng/μl, manufactured by Takara Shuzo) were added for denaturing at65° C. for 10 minutes, followed by quenching on ice. To the resultingsolution, 6 μl of a buffer attached to SuperScript II (manufactured byLifetechnologies), 3 μl of 0.1 mol/l DTT, 1.5 μl of dNTPs (25 mmol/ldATP, 25 mmol/l dCTP, 25 mmol/l dGTP, 10 mmol/l dTTP), 1.5 μl ofCy5-dUTP or Cy3-dUTP (manufactured by NEN) and 2 μl of SuperScript IIwere added, and allowed to stand at 25° C. for 10 minutes and then at42° C. for 110 minutes. The RNA extracted from the cells using glucoseas the carbon source and the RNA extracted from the cells using ammoniumacetate were labeled with Cy5-dUTP and Cy3-dUTP, respectively. After thefluorescence labeling reaction, the RNA was digested by adding 1.5 μl of1 mol/l sodium hydroxide-20 mmol/l EDTA solution and 3.0 μl of 10% SDSsolution, and allowed to stand at 65° C. for 10 minutes. The two cDNAsolutions after the labeling were mixed and purified using Qiagen PCRpurification Kit (manufactured by QIAGEN) according to the manufacture'sinstructions to give a volume of 10 μl.

(3) Hybridization

UltraHyb (110 μl) (manufactured by Ambion) and the fluorescence-labeledcDNA solution (10 μl) were mixed and subjected to hybridization and thesubsequent washing of slide glass using GeneTAC Hybridization Station(manufactured by Genomic Solutions) according to the manufacture'sinstructions. The hybridization was carried out at 50° C., and thewashing was carried out at 25° C.

(4) Fluorescence Analysis

The fluorescence amount of each DNA array having the fluorescent cDNAhybridized therewith was measured using ScanArray 4000 (manufactured byGSI Lumonics).

Table 5 shows the Cy3 and Cy5 signal intensities of the genes havingbeen corrected on the basis of the data of the rabbit globin used as theinternal standard and the Cy3/Cy5 ratios.

TABLE 5 SEQ ID NO Cy3 intensity Cy5 intensity Cy3/Cy5 207 5248 3240 1.623433 2239 2694 0.83 281 2370 2595 0.91 3435 2566 2515 1.02 3439 55976944 0.81 765 6134 4943 1.24 3455 1169 1284 0.91 1226 1301 1493 0.871229 1168 1131 1.03 3448 1187 1594 0.74 3451 2845 3859 0.74 3453 34981705 2.05 3455 1491 1144 1.30 1743 1972 1841 1.07 3470 4752 3764 1.262132 1173 1085 1.08 3476 1847 1420 1.30 3477 1284 1164 1.10 3485 45398014 0.57 3488 34289 1398 24.52 3489 43645 1497 29.16 3494 3199 25031.28 3496 3428 2364 1.45 3497 3848 3358 1.15

The ORF function data estimated by using software were searched for SEQID NOS:3488 and 3489 showing remarkably strong Cy3 signals. As a result,it was found that SEQ ID NOS:3488 and 3489 are a maleate synthase geneand an isocitrate lyase gene, respectively. It is known that these genesare transcriptionally induced by acetic acid in Corynebacteriumglutamicum (Archives of Microbiology, 168: 262-269 (1997)).

As described above, a gene of which expression is fluctuates could bediscovered by synthesizing appropriate oligo DNA primers based on theORF nucleotide sequence information deduced from the full genomicnucleotide sequence information of Corynebacterium glutamicum ATCC 13032using software, amplifying the nucleotide sequences of the gene usingthe genome DNA of Corynebacterium glutamicum as a template in the PCRreaction, and thus producing and using a DNA microarray.

This Example shows that the expression amount can be analyzed using aDNA microarray in the 24 genes. On the other hand, the present DNAmicroarray techniques make it possible to prepare DNA microarrays havingthereon several thousand gene probes at once. Accordingly, it is alsopossible to prepare DNA microarrays having thereon all of the ORF geneprobes deduced from the full genomic nucleotide sequence ofCorynebacterium glutamicum ATCC 13032 determined by the presentinvention, and analyze the expression profile at the total gene level ofCorynebacterium glutamicum using these arrays.

EXAMPLE 5

Homology Search Using Corynebacterium glutamicum Genome Sequence

(1) Search of Adenosine Deaminase

The amino acid sequence (ADD_(—) ECOLI) of Escherichia coli adenosinedeaminase was obtained from Swiss-prot Database as the amino acidsequence of the protein of which function had been confirmed asadenosine deaminase (EC3.5.4.4). By using the full length of this aminoacid sequence as a query, a homology search was carried out on anucleotide sequence database of the genome sequence of Corynebacteriumglutamicum or a database of the amino acids in the ORF region deducedfrom the genome sequence using FASTA program (Proc. Natl. Acad. Sci.ISA, 85: 2444-2448 (1988)). A case where E-value was le⁻¹⁰ or less wasjudged as being significantly homologous. As a result, no sequencesignificantly homologous with the Escherichia coli adenosine deaminasewas found in the nucleotide sequence database of the genome sequence ofCorynebacterium glutamicum or the database of the amino acid sequencesin the ORF region deduced from the genome sequence. Based on theseresults, it is assumed that Corynebacterium glutamicum contains no ORFhaving adenosine deaminase activity and thus has no activity ofconverting adenosine into inosine.

(2) Search of Glycine Cleavage Enzyme

The sequences (GCSP_(—) ECOLI, GCST_(—) ECOLI and GCSH_(—) ECOLI) ofglycine decarboxylase, aminomethyl transferase and an aminomethyl groupcarrier each of which is a component of Escherichia coli glycinecleavage enzyme as the amino acid sequence of the protein, of whichfunction had been confirmed as glycine cleavage enzyme (EC2.1.2.10),were obtained from Swiss-prot Database.

By using these full-length amino acid sequences as a query, a homologysearch was carried out on a nucleotide sequence database of the genomesequence of Corynebacterium glutamicum or a database of the ORF aminoacid sequences deduced from the genome sequence using FASTA program. Acase where E-value was le⁻¹⁰ or less was judged as being significantlyhomologous. As a result, no sequence significantly homologous with theglycine decarboxylase, the aminomethyl transferase or the aminomethylgroup carrier each of which is a component of Escherichia coli glycinecleavage enzyme, was found in the nucleotide sequence database of thegenome sequence of Corynebacterium glutamicum or the database of the ORFamino acid sequences estimated from the genome sequence. Based on theseresults, it is assumed that Corynebacterium glutamicum contains no ORFhaving the activity of glycine decarboxylase, aminomethyl transferase orthe aminomethyl group carrier and thus has no activity of the glycinecleavage enzyme.

(3) Search of IMP Dehydrogenase

The amino acid sequence (IMDH ECOLI) of Escherichia coli IMPdehydrogenase as the amino acid sequence of the protein, of whichfunction had been confirmed as IMP dehydrogenase (EC1.1.1.205), wasobtained from Swiss-prot Database. By using the full length of thisamino acid sequence as a query, a homology search was carried out on anucleotide sequence database of the genome sequence of Corynebacteriumglutamicum or a database of the ORF amino acid sequences predicted fromthe genome sequence using FASTA program. A case where E-value was le⁻¹⁰or less was judged as being significantly homologous. As a result, theamino acid sequences encoded by two ORFs, namely, an ORF positioned inthe region of the nucleotide sequence No. 615336 to 616853 (or ORFhaving the nucleotide sequence represented by SEQ ID NO:672) and anotherORF positioned in the region of the nucleotide sequence No. 616973 to618094 (or ORF having the nucleotide sequence represented by SEQ IDNO:674) were significantly homologous with the ORFs of Escherichia coliIMP dehydrogenase. By using the above-described predicted amino acidsequence as a query in order to examine the similarity of the amino acidsequences encoded by the ORFs with IMP dehydrogenases of other organismsin greater detail, a search was carried out on GenBank(http://www.ncbi.nlm.nih.gov/) nr-aa database (amino acid sequencedatabase constructed on the basis of GenBankCDS translation products,PDB database, Swiss-Prot database, PIR database, PRF database byeliminating duplicated registrations) using BLAST program. As a result,both of the two amino acid sequences showed significant homologies withIMP dehdyrogenases of other organisms and clearly higher homologies withIMP dehdyrogenases than with amino acid sequences of other proteins, andthus, it was assumed that the two ORFs would function as IMPdehydrogenase. Based on these results, it was therefore assumed thatCorynebacterium glutamicum has two ORFs having the IMP dehydrogenaseactivity.

EXAMPLE 6

Proteome Analysis of Proteins Derived from Corynebacterium glutamicum

(1) Preparations of Proteins Derived from Corynebacterium glutamicumATCC 13032, FERM BP-7134 and FERM BP-158

Culturing tests of Corynebacterium glutamicum ATCC 13032 (wild typestrain), Corynebacterium glutamicum FERM BP-7134 (lysine-producingstrain) and Corynebacterium glutamicum (FERM BP-158, lysine-highlyproducing strain) were carried out in a 5 l jar fermenter according tothe method in Example 2(3). The results are shown in Table 6.

TABLE 6 Strain L-Lysine yield (g/l) ATCC 13032 0 FERM BP-7134 45 FERMBP-158 60

After culturing, cells of each strain were recovered by centrifugation.These cells were washed with Tris-HCl buffer (10 mmol/l Tris-HCl, pH6.5, 1.6 mg/ml protease inhibitor (COMPLETE; manufactured by BoehringerMannheim)) three times to give washed cells which could be stored underfreezing at −80° C. The freeze-stored cells were thawed before use, andused as washed cells.

The washed cells described above were suspended in a disruption buffer(10 mmol/l Tris-HCl, pH 7.4, 5 mmol/l magnesium chloride, 50 mg/l RNase,1.6 mg/ml protease inhibitor (COMPLETE: manufactured by BoehringerMannheim)), and disrupted with a disrupter (manufactured by Brown) undercooling. To the resulting disruption solution, DNase was added to give aconcentration of 50 mg/l, and allowed to stand on ice for 10 minutes.The solution was centrifuged (5,000×g, 15 minutes, 4° C.) to remove theundisrupted cells as the precipitate, and the supernatant was recovered.

To the supernatant, urea was added to give a concentration of 9 mol/l,and an equivalent amount of a lysis buffer (9.5 mol/l urea, 2% NP-40, 2%Ampholine, 5% mercaptoethanol, 1.6 mg/ml protease inhibitor (COMPLETE;manufactured by Boehringer Mannheim) was added thereto, followed bythoroughly stirring at room temperature for dissolving.

After being dissolved, the solution was centrifuged at 12,000×g for 15minutes, and the supernatant was recovered.

To the supernatant, ammonium sulfate was added to the extent of 80%saturation, followed by thoroughly stirring for dissolving.

After being dissolved, the solution was centrifuged (16,000×g, 20minutes, 4° C.), and the precipitate was recovered. This precipitate wasdissolved in the lysis buffer again and used in the subsequentprocedures as a protein sample. The protein concentration of this samplewas determined by the method for quantifying protein of Bradford.

(2) Separation of Protein by Two Dimensional Electrophoresis

The first dimensional electrophoresis was carried out as described belowby the isoelectric electrophoresis method.

A molded dry IPG strip gel (pH 4-7, 13 cm, Immobiline DryStrips;manufactured by Amersham Pharmacia Biotech) was set in anelectrophoretic apparatus (Multiphor II or IPGphor; manufactured byAmersham Pharmacia Biotech) and a swelling solution (8 mol/l urea, 0.5%Triton X-100, 0.69 dithiothreitol, 0:5% Ampholine, pH 3-10) was packedtherein, and the gel was allowed to stand for swelling 12 to 16 hours.

The protein sample prepared above was dissolved in a sample solution (9mol/l urea, 2% CRAPS, 1% dithiothreitol, 2% Ampholine, pH 3-10), andthen about 100 to 500 μg (in terms of protein) portions thereof weretaken and added to the swollen IPG strip gel.

The electrophoresis was carried out in the 4 steps as defined belowunder controlling the temperature to 20° C.:

-   step 1: 1 hour under a gradient mode of 0 to 500V;-   step 2: 1 hour under a gradient mode of 500 to 1,000 V;-   step 3: 4 hours under a gradient mode of 1,000 to 8,000 V; and-   step 4: 1 hour at a constant voltage of 8,000 V.

After the isoelectric electrophoresis, the IPG strip gel was put offfrom the holder and soaked in an equilibration buffer A (50 mmol/lTris-HCl, pH 6.8, 30% glycerol, 1% SDS, 0.25% dithiothreitol) for 15minutes and another equilibration buffer B (50 mmol/l Tris-HCl, pH 6.8,6 mol/l urea, 30% glycerol, 1% SDS, 0.45% iodo acetamide) for 15 minutesto sufficiently equilibrate the gel.

After the equilibrium, the IPG strip gel was lightly rinsed in an SDSelectrophoresis buffer (1.4% glycine, 0.1% SDS, 0.3% Tris-HCl, pH 8.5),and the second dimensional electrophoresis depending on molecular weightwas carried out as described below to separate the proteins.

Specifically, the above IPG strip gel was closely placed on 14%polyacrylamide slub gel (14% polyacrylamide, 0.37% bisacrylamide, 37.5mmol/l Tris-HCl, pH 8.8, 0.1% SDS, 0.1% TEMED, 0.1% ammonium persulfate)and subjected to electrophoresis under a constant voltage of 30 mA at20° C. for 3 hours to separate the proteins.

(3) Detection of Protein Spot

Coomassie staining was performed by the method of Gorg et al.(Electrophoresis, 9: 531-546 (1988)) for the slub gel after the seconddimensional electrophoresis. Specifically, the slub gel was stainedunder shaking at 25° C. for about 3 hours, the excessive coloration wasremoved with a decoloring solution, and the gel was thoroughly washedwith distilled water.

The results are shown in FIG. 2. The proteins derived from the ATCC13032 strain (FIG. 2A), FERM BP-7134 strain (FIG. 2B) and FERM BP-158strain (FIG. 2C) could be separated and detected as spots.

(4) In-Gel Digestion of Detected Protein Spot

The detected spots were each cut out from the gel and transferred intosiliconized tube, and 400 μl of 100 mmol/l ammonium bicarbonate :acetonitrile solution (1:1, v/v) was added thereto, followed by shakingovernight and freeze-dried as such. To the dried gel, 10 μl of alysylendopeptidase (LysC) solution (manufactured by WAKO, prepared with0.1% SDS-containing 50 mmol/l ammonium bicarbonate to give aconcentration of 100 ng/μl) was added and the gel was allowed to standfor swelling at 0° C. for 45 minutes, and then allowed to stand at 37°C. for 16 hours. After removing the LysC solution, 20 μl of anextracting solution (a mixture of 60% acetonitrile and 5% formic acid)was added, followed by ultrasonication at room temperature for 5 minutesto disrupt the gel. After the disruption, the extract was recovered bycentrifugation (12,000 rpm, 5 minutes, room temperature). This operationwas repeated twice to recover the whole extract. The recovered extractwas concentrated by centrifugation in vacuo to halve the liquid volume.To the concentrate, 20 μl of 0.1% trifluoroacetic acid was added,followed by thoroughly stirring, and the mixture was subjected todesalting using ZipTip (manufactured by Millipore). The protein absorbedon the carriers of ZipTip was eluted with 5 μl ofα-cyano-4-hydroxycinnamic acid for use as a sample solution foranalysis.

(5) Mass Spectrometry and Amino Acid Sequence Analysis of Protein Spotwith Matrix Assisted Laser Desorption Ionization Time of Flight MassSpectrometer (MALDI-TOFMS)

The sample solution for analysis was mixed in the equivalent amount witha solution of a peptide mixture for mass calibration (300 nmol/lAngiotensin II, 300 nmol/l Neurotensin, 150 nmol/l ACTHclip 18-39, 2.3μmol/l bovine insulin B chain), and 1 μl of the obtained solution wasspotted on a stainless probe and crystallized by spontaneously drying.

As measurement instruments, REFLEX MALDI-TOF mass spectrometer(manufactured by Bruker) and an N2 laser (337 nm) were used incombination.

The analysis by PMF (peptide-mass finger printing) was carried out usingintegration spectra data obtained by measuring 30 times at anaccelerated voltage of 19.0 kV and a detector voltage of 1.50 kV underreflector mode conditions. Mass calibration was carried out by theinternal standard method.

The PSD (post-source decay) analysis was carried out using integrationspectra obtained by successively altering the reflection voltage and thedetector voltage at an accelerated voltage of 27.5 kV.

The masses and amino acid sequences of the peptide fragments derivedfrom the protein spot after digestion were thus determined.

(6) Identification of Protein Spot

From the amino acid sequence information of the digested peptidefragments derived from the protein spot obtained in the above (5), ORFscorresponding to the protein were searched on the genome sequencedatabase of Corynebacterium glutamicum ATCC 13032 as constructed inExample 1 to identify the protein.

The identification of the protein was carried out using MS-Fit programand MS-Tag program of intranet protein prospector.

(a) Search and Identification of Gene Encoding High-Expression Protein

In the proteins derived from Corynebacterium glutamic ATCC 13032 showinghigh expression amounts in CBB-staining shown in FIG. 2A, the proteinscorresponding to Spots-1, 2, 3, 4 and 5 were identified by the abovemethod.

As a result, it was found that Spot-1 corresponded to enolase which wasa protein having the amino acid sequence of SEQ ID NO:4585; Spot-2corresponded to phosphoglycelate kinase which was a protein having theamino acid sequence of SEQ ID NO:5254; Spot-3 corresponded toglyceraldehyde-3-phosphate dehydrogenase which was a protein having theamino acid sequence represented by SEQ ID NO:5255; Spot-4 correspondedto fructose bis-phosphate aldolase which was a protein having the aminoacid sequence represented by SEQ ID NO:6543; and Spot-5 corresponded totriose phosphate isomerase which was a protein having the amino acidsequence represented by SEQ ID NO:5252.

These genes, represented by SEQ ID NOS:1085, 1754, 1775, 3043 and 1752encoding the proteins corresponding to Spots-1, 2, 3, 4 and 5,respectively, encoding the known proteins are important in the centralmetabolic pathway for maintaining the life of the microorganism.Particularly, it is suggested that the genes of Spots-2, 3 and 5 form anoperon and a high-expression promoter is encoded in the upstream thereof(J. of Bacteriol., 174: 6067-6086 (1992)).

Also, the protein corresponding to Spot-9 in FIG. 2 was identified inthe same manner as described above, and it was found that Spot-9 was anelongation factor Tu which was a protein having the amino acid sequencerepresented by SEQ ID NO:6937, and that the protein was encoded by DNAhaving the nucleotide sequence represented by SEQ ID NO:3437.

Based on these results, the proteins having high expression level wereidentified by proteome analysis using the genome sequence database ofCorynebacterium glutamicum constructed in Example 1. Thus, thenucleotide sequences of the genes encoding the proteins and thenucleotide sequences upstream thereof could be searched simultaneously.Accordingly, it is shown that nucleotide sequences having a function asa high-expression promoter can be efficiently selected.

(b) Search and Identification of Modified Protein

Among the proteins derived from Corynebacterium glutamicum FERM BP-7134shown in FIG. 2B, Spots-6, 7 and 8 were identified by the above method.As a result, these three spots all corresponded to catalase which was aprotein having the amino acid sequence represented by SEQ ID NO:3785.

Accordingly, all of Spots-6, 7 and 8 detected as spots differing inisoelectric mobility were all products derived from a catalase genehaving the nucleotide sequence represented by SEQ ID NO:285.Accordingly, it is shown that the catalase derived from Corynebacteriumglutamicum FERM BP-7134 was modified after the translation.

Based on these results, it is confirmed that various modified proteinscan be efficiently searched by proteome analysis using the genomesequence database of Corynebacterium glutamicum constructed in Example1.

(c) Search and Identification of Expressed Protein Effective in LysineProduction

It was found out that in FIG. 2A (ATCC 13032: wild type strain), FIG. 2B(FERM BP-7134: lysine-producing strain) and FIG. 2C (FERM BP-158:lysine-highly producing strain), the catalase corresponding to Spot-8and the elongation factor Tu corresponding to Spot-9 as identified aboveshowed the higher expression level with an increase in the lysineproductivity.

Based on these results, it was found that hopeful mutated proteins canbe efficiently searched and identified in breeding aiming atstrengthening the productivity of a target product by the proteomeanalysis using the genome sequence database of Corynebacteriumglutamicum constructed in Example 1.

Moreover, useful mutation points of useful mutants can be easilyspecified by searching the nucleotide sequences (nucleotide sequences ofpromoter, ORF, or the like) relating to the identified proteins, usingthe above database and using primers designed on the basis of thesequences. As a result of the fact that the mutation points arespecified, industrially useful mutants which have the useful mutationsor other useful mutations derived therefrom can be easily bred.

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one of skill in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof. All references cited hereinare incorporated in their entirety.

1. An isolated DNA encoding a polypeptide having homoserinedehydrogenase activity, comprising an amino acid sequence of homoserinedehydrogenase derived from a microorganism belonging to the genusCorynebacterium in which the Val residue at the position correspondingto the 59th position in the amino acid sequence of SEQ ID NO:6952 isreplaced with an amino acid residue other than a Val residue, or apolypeptide comprising an amino acid sequence in which the Val residueat the 59th position in the amino acid sequence of SEQ ID NO:6952 isreplaced with an amino acid residue other than a Val residue, whereinthe Val residue at the 59th position is optionally replaced with an Alaresidue.
 2. An isolated transformed host cell, wherein the host cell isoptionally a coryneform bacterium, comprising the DNA of claim
 1. 3. Anisolated transformed host cell, wherein the host cell is optionally acoryneform bacterium, comprising in its chromosome the DNA of claim 1.4. The transformed host cell according to claim 2, wherein the host cellis a Corynebacterium glutamicum.
 5. The transformed host cell accordingto claim 3, wherein the host cell is a Corynebacterium glutamicum.
 6. Amethod for producing L-lysine, comprising: culturing the transformedhost cell of any one of claims 4 or 5 in a medium to produce andaccumulate L-lysine in the medium, and recovering the L-lysine from theculture.